High reliability analyte sensor integrated with temperature detection

Abstract

The invention discloses a high-reliability analyte sensor integrated with temperature detection, which comprises at least one layer of substrate, at least two electrodes, pins and a temperature sensor, and the temperature sensor is arranged on the surface of an in-vivo part and is used for directly detecting the in-vivo temperature of a patient, so that the detected temperature does not need to be further calibrated, a temperature treatment process is omitted, and the detection efficiency is improved. The reliability of the detected temperature is improved; meanwhile, at least one protective layer is arranged on the surface of the substrate, the protective layer at least covers the edge of the electrode and / or the temperature sensor, the adhesion between the edge of the electrode and / or the temperature sensor and the substrate is increased, the edge of the electrode is prevented from warping, bubbling and falling off, meanwhile, the protective layer can also increase the mechanical strength of the substrate of the sensor, the service life of the sensor is prolonged, and the reliability of the sensor is improved. And the detection reliability of the sensor is improved.

Description

Technical Field

[0001] The present invention relates generally to the field of medical devices, and more particularly to a high-reliability analyte sensor with integrated temperature detection. Background Art

[0002] The pancreas in a normal person's body can automatically monitor the glucose content in the human blood and automatically secrete the required insulin / glucagon. However, the pancreas of diabetic patients has abnormal function and cannot normally secrete the insulin required by the human body. Therefore, diabetes is a metabolic disease caused by abnormal pancreatic function in the human body, and diabetes is a lifelong disease. At present, medical technology cannot cure diabetes, and can only control the occurrence and development of diabetes and its complications by stabilizing blood sugar.

[0003] Diabetic patients need to test their blood sugar before injecting insulin into their bodies. Currently, most detection methods can continuously detect blood sugar and send blood sugar data to remote devices in real time for users to view. This detection method is called continuous glucose monitoring (CGM). This method requires the detection device to be attached to the surface of the skin, and the probe it carries is inserted into the subcutaneous tissue fluid to complete the detection. According to the detected blood sugar value, relevant algorithms, such as PID algorithm and MPC algorithm, are used to calculate the amount of insulin that needs to be infused into the patient's body. Excessive insulin infusion may cause hypoglycemia in patients, and insufficient insulin infusion may also maintain the patient's blood sugar at a high level, causing hyperglycemia. Therefore, the accuracy of the insulin infusion amount is crucial to maintaining the patient's blood sugar stability, and the amount of insulin infused is directly related to the blood sugar value in the patient's body. Therefore, the accuracy of the blood sugar measurement value is crucial to maintaining the patient's blood sugar stability.

[0004] Since changes in temperature affect the permeability of the sensor membrane and the activity of active enzymes, it is generally believed that temperature also affects the sensitivity of the sensor. The temperature of the sensor when it leaves the factory or is calibrated is likely to be different from the temperature during actual use, that is, when it is in the user's body. Therefore, in order to ensure the accuracy of blood glucose measurement values, it is necessary to consider the influence of temperature during measurement.

[0005] At present, some existing technologies integrate temperature sensors on transmitters to measure ambient temperature, while others integrate sensors on a shell close to the skin to measure skin temperature. However, none of these methods directly measures the temperature of the sensor when it is actually used, that is, the body temperature when the sensor is inserted into the body. The temperature measured according to the methods in the existing technologies needs to be further processed by temperature compensation, algorithm correction, etc. On the one hand, the processing process is complicated, and on the other hand, the processing results may not be accurate and reliable. Moreover, in the existing technologies, electrodes, temperature sensors, and pins are generally fixed on the sensor substrate by welding or pasting processes, while electrodes and pins are made of conductive materials, and the substrate is made of insulating materials. The materials of electrodes, temperature sensors, pins, and substrates are inconsistent. During use, the edges of electrodes, temperature sensors, and pins often warp, bubble, or even fall off, affecting the detection reliability and service life of the sensor.

[0006] Therefore, the prior art urgently needs an analyte sensor that can directly detect the operating temperature of the sensor, improve detection reliability and extend service life. Summary of the invention

[0007] In view of the shortcomings of the above-mentioned prior art, an embodiment of the present invention discloses a high-reliability analyte sensor with integrated temperature detection. The temperature sensor is arranged on the surface of the inner part of the substrate, and can directly measure the temperature of the analyte sensor during in vivo detection. There is no need to further calibrate the detected temperature, omitting the temperature processing process, thereby improving the reliability of the detected temperature. According to the detected in vivo temperature, the analyte value can be directly calibrated to improve the accuracy of analyte detection. At the same time, at least one protective layer is arranged on the surface of the substrate, and the protective layer at least covers the edges of the electrode and / or the temperature sensor, thereby increasing the adhesion between the edges of the electrode and / or the temperature sensor and the substrate, and preventing the edges of the electrode from warping, bubbling, and falling off. At the same time, the protective layer can also increase the mechanical strength of the sensor substrate, thereby extending the service life of the sensor and improving the detection reliability of the sensor.

[0008] The present invention discloses an analyte sensor, comprising: at least one substrate, including an internal part and an external part; at least two electrodes, arranged on the surface of the internal part, for piercing subcutaneously to obtain analyte parameter information; pins, arranged on the surface of the external part, respectively electrically connected to corresponding electrodes through wires; and a temperature sensor, arranged on the surface of the internal part, for directly detecting the internal temperature of a patient; wherein at least one protective layer is arranged on the surface of the substrate, and the protective layer at least covers the edges of the two electrodes and / or the temperature sensor.

[0009] According to one aspect of the present invention, the protection layer also covers the edges of the pins.

[0010] According to one aspect of the present invention, the thickness of the protective layer is 1-20 um.

[0011] According to one aspect of the present invention, the material of the protective layer is 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 present invention, a liquid polyimide protective layer is further provided on the temperature sensor before providing the protective layer.

[0013] According to one aspect of the present invention, the temperature sensor is one of a metal thin film thermal resistor, a carbon thin film resistor, a metal oxide thin film thermal resistor, and an alloy thin film thermal resistor.

[0014] According to one aspect of the present invention, the temperature sensor is a thin film platinum thermal resistor.

[0015] According to one aspect of the present invention, the at least two electrodes include at least a working electrode and a counter electrode.

[0016] According to one aspect of the present invention, the working electrode and the temperature sensor are at the same depth of penetration into the subcutaneous tissue.

[0017] According to one aspect of the present invention, at least one substrate is a single-layer substrate, and the working electrode and the temperature sensor are arranged in parallel on the same surface of the single-layer substrate.

[0018] According to one aspect of the present invention, at least one substrate is a single-layer substrate, and the working electrode and the temperature sensor are arranged on different surfaces of the single-layer substrate.

[0019] According to one aspect of the present invention, at least one substrate comprises a multi-layer substrate, and the working electrode and the temperature sensor are arranged in parallel on the same surface of the same layer of substrate.

[0020] According to one aspect of the present invention, the at least one substrate comprises a multi-layer substrate, and the working electrode and the temperature sensor are arranged on different surfaces of the same layer of substrate.

[0021] According to one aspect of the present invention, the at least one substrate comprises a multi-layer substrate, and the working electrode and the temperature sensor are arranged on different surfaces of substrates of different layers.

[0022] According to one aspect of the present invention, the working electrode and the temperature sensor are arranged on different surfaces of adjacent substrates at different levels.

[0023] According to one aspect of the present invention, the working electrode and the temperature sensor are arranged on different surfaces of a spaced-apart substrate at different levels.

[0024] According to one aspect of the present invention, the multi-layered substrate is prefabricated and glued together into a whole.

[0025] According to one aspect of the present invention, the temperature sensor is embedded in the working electrode or the counter electrode.

[0026] According to one aspect of the present invention, the conductive lines are disposed on the surface of the substrate.

[0027] According to one aspect of the present invention, the conductive line is disposed in an inner layer of the substrate.

[0028] According to one aspect of the present invention, at least one layer of insulating material is disposed behind at least one area of ​​the substrate surface, the insulating material avoiding the pin area, the electrode and the central conductive area of ​​the temperature sensor.

[0029] Compared with the prior art, the technical solution of the present invention has the following advantages:

[0030] The high-reliability analyte sensor with integrated temperature detection disclosed by the present invention has a temperature sensor arranged on the surface of the inner part of the substrate, and can directly measure the temperature of the analyte sensor during in vivo detection, without further calibration of the detected temperature, omitting the temperature processing process, thereby improving the reliability of the detected temperature, and further, according to the detected in vivo temperature, directly calibrating the analyte value, thereby improving the accuracy of analyte detection; at the same time, at least one protective layer is arranged on the surface of the substrate, and the protective layer at least covers the edge of the electrode and / or the temperature sensor, thereby increasing the adhesion between the edge of the electrode and / or the temperature sensor and the substrate, and preventing the edge of the electrode from warping, bubbling, and falling off, and at the same time, the protective layer can also increase the mechanical strength of the sensor substrate, thereby extending the service life of the sensor and improving the detection reliability of the sensor.

[0031] Furthermore, the protective layer also covers the edges of the pins and avoids the central area of ​​the pins to prevent the edges of the pins from warping, bubbling or falling off, thereby increasing the mechanical strength of the sensor substrate and extending the service life of the sensor.

[0032] Furthermore, after the protective layer covers the edge of the electrode, since the protective layer is thicker than the electron conduction layer of the electrode, the protective layer can form pits on the electron conduction layer. Compared with the existing scheme, the pits can accommodate a larger volume of anti-interference layer, enzyme layer, regulation layer and biocompatible layer, thereby improving the sensitivity of the electrode.

[0033] Furthermore, after the protective layer covers the edge of the temperature sensor, the protective layer can also enhance the adhesion between the aluminum oxide insulating layer and the substrate, prevent the insulating layer from warping and bubbling, and improve the temperature detection reliability of the sensor.

[0034] Furthermore, the protective layer is made of the same material as the substrate and has consistent physical properties, which can prevent the protective layer from being damaged or falling off due to uneven stress or stress concentration on the substrate.

[0035] Furthermore, the temperature sensor and at least one electrode may be arranged in parallel or in sequence on the surface of the internal body part, making full use of the area of ​​the substrate and facilitating the miniaturization of the analyte sensor.

[0036] Furthermore, the temperature sensor and at least one electrode are arranged on different surfaces of the substrate, and the temperature sensor and the electrode can be designed with a larger area, thereby improving the reliability of analyte detection and temperature detection.

[0037] Furthermore, the working electrode and the temperature sensor are at the same depth of penetration under the skin, and the operating environment of the temperature sensor is the same as that of the working electrode. Therefore, the temperature measured by the temperature sensor is the operating temperature of the working electrode. There is no need to further compensate for the measured temperature, making the blood glucose measurement value more accurate.

[0038] Furthermore, the outer layer of the temperature sensor is coated with a liquid polyimide insulating layer as a protective layer, which can reduce or eliminate the stress influence of different material layers and prevent the temperature sensor from being damaged due to uneven stress or stress concentration.

[0039] Furthermore, the substrate includes at least two levels of substrate, and at least two electrodes and temperature sensors are arranged on different layers of sub-substrates. On the one hand, the distance between the electrodes and between the electrodes and the temperature sensors can be increased, the signal interference between the electrodes and between the electrodes and the temperature sensors can be reduced, and the reliability of analyte detection and temperature detection can be improved; on the other hand, the electrodes or temperature sensors on each level of substrate can be set to a larger area, and the electrodes or temperature sensors with a larger area can be in more complete contact with the body fluid, and the signals can be more stable, thereby improving the reliability of analyte detection and temperature detection.

[0040] Furthermore, different layers of sub-substrates can be prefabricated first, that is, electrodes, wires and pins are prefabricated on each layer of the substrate, and then pasted and combined into a whole to form a complete sensor. Different from the conventional layer-by-layer coating process, it can avoid insulation failure caused by brittle cracking due to insufficient curing of the substrate material, and further cause crosstalk in the electrical signals between the wires or electrodes, and noise in the detection signal, thereby improving the detection reliability of the sensor.

[0041] Furthermore, at least one layer of insulating material is provided behind at least one area on the sensor substrate, and the insulating material avoids the areas where the pins, electrodes and temperature sensors are located, thereby increasing the mechanical strength of the sensor substrate. After the sensor is inserted into the subcutaneous tissue, when it bends or bends with muscle peristalsis, the time it takes for the substrate to reach extreme fatigue is prolonged, thereby extending the service life of the sensor and thereby improving the reliability of the sensor's analyte detection and temperature detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1a to Figure 1eSchematic diagram of an analyte sensor in which a temperature sensor and an electrode are located on the same surface of a substrate in an embodiment of the present invention;

[0043] Figure 2a-2k A schematic diagram of an analyte sensor in which at least one electrode and a temperature sensor are located on different surfaces of a substrate according to an embodiment of the present invention;

[0044] Figure 3a-3f A schematic diagram of an analyte sensor with an integrated temperature sensor having an insulating material disposed thereafter in an embodiment of the present invention;

[0045] Figures 4a-4f Schematic diagram of an analyte sensor of an integrated temperature sensor provided with a protective layer according to an embodiment of the present invention. DETAILED DESCRIPTION

[0046] As mentioned above, the temperature sensors in the prior art cannot directly detect the temperature during electrode operation. The detected temperature needs to be further processed, and the processing process is complicated. The processing results may not be accurate and reliable. Moreover, since the materials of the electrodes, temperature sensors, pins and substrates are inconsistent, the edges of the electrodes, temperature sensors and pins often warp, bubble or even fall off during use, affecting the detection reliability and service life of the sensor.

[0047] In order to solve this problem, the present invention provides a high-reliability analyte sensor with integrated temperature detection. The temperature sensor is arranged on the surface of the inner part of the substrate, and can directly measure the temperature of the analyte sensor during in vivo detection. There is no need to further calibrate the detected temperature, omitting the temperature processing process, thereby improving the reliability of the detected temperature. Further, based on the detected in vivo temperature, the analyte value can be directly calibrated to improve the accuracy of analyte detection. At the same time, at least one protective layer is arranged on the surface of the substrate, and the protective layer at least covers the edges of the electrode and / or the temperature sensor, thereby increasing the adhesion between the edges of the electrode and / or the temperature sensor and the substrate, and preventing the edges of the electrode from warping, bubbling, and falling off. At the same time, the protective layer can also increase the mechanical strength of the sensor substrate, thereby extending the service life of the sensor and improving the detection reliability of the sensor.

[0048] Various exemplary embodiments of the present invention will now be described in detail with reference to the accompanying drawings. It should be understood that the relative arrangement of components and steps, numerical expressions and numerical values ​​set forth in these embodiments should not be construed as limiting the scope of the present invention unless otherwise specifically stated.

[0049] In addition, it should be understood that for ease of description, the sizes of the various components shown in the drawings are not necessarily drawn according to actual proportions. For example, the thickness, width, length or distance of certain units may be enlarged relative to other structures.

[0050] The following description of the exemplary embodiments is merely illustrative and is not intended to limit the present invention and its application or use in any sense. Techniques, methods and devices known to ordinary technicians in the relevant field may not be discussed in detail here, but where applicable, these techniques, methods and devices should be considered as part of this specification.

[0051] It should be noted that like reference numerals and letters refer to similar items in the following figures, and thus, once an item is defined or described in one figure, it will not require further discussion in the subsequent figure descriptions.

[0052] In addition, it should be understood that one or more method steps mentioned in the present invention do not exclude the existence of other method steps before or after the combination step or the insertion of other method steps between these explicitly mentioned steps, unless otherwise specified; it should also be understood that the combination connection relationship between one or more devices / apparatuses mentioned in the present invention does not exclude the existence of other devices / apparatuses before or after the combination device / apparatus or the insertion of other devices / apparatuses between these explicitly mentioned two devices / apparatuses, unless otherwise specified. Moreover, unless otherwise specified, the numbering of each method step is only a convenient tool for identifying each method step, and is not intended to limit the order of arrangement of each method step or the scope of the present invention. Changes or adjustments in their relative relationships should also be regarded as the scope of the present invention without substantially changing the technical content.

[0053] Embodiment 1

[0054] Figure 1a to Figure 1d Schematic diagram of an analyte sensor in which a temperature sensor and an electrode are located on the same surface of a substrate in an embodiment of the present invention.

[0055] Reference Figure 1a , in order to conveniently and clearly demonstrate the structural features of sensor 11, Figure 1a The length, width, thickness and curve characteristics of the sensor are expressed in an exaggerated form. The actual length, width, thickness and curve characteristics of the sensor may be different from the illustration.

[0056] In other illustrations in this article, the sensor length, width, thickness and curve characteristics are also expressed in an exaggerated form. The actual length, width, thickness and curve characteristics of the sensor may be different from the illustrations, which will not be repeated below.

[0057] Similarly, the wires, pin electrodes and temperature sensors described above and below are also expressed in exaggerated form in the diagrams. The wires, pins and electrodes in the diagrams are only auxiliary examples for expressing the scheme of the present invention and are not completely equivalent to the wires, pins and wires in the actual sensor. For example, the wires in the actual sensor are flat wires with a certain width, while the wires in the diagrams are shown in the form of lines.

[0058] The sensor 11 includes a substrate 111, Figure 1a The dotted line is a dividing line, and the substrate 111 is divided into an external part X and an internal part Y. Electrodes are laid on the internal part Y, including at least one working electrode 1131 (W) and at least one additional electrode. Obviously, in this embodiment, the additional electrode includes a counter electrode 1231 (C) and a reference electrode 1331 (R), thereby forming a three-electrode system. The counter electrode 1231 is the other pole relative to the working electrode 1131, and forms a closed loop with the working electrode 1131, so that the current on the electrode can be normally conducted. The reference electrode 1331 is used to provide a reference potential for the working electrode 1131, so that the detection potential can be effectively controlled. Pins are laid on the external part X, and the pins correspond to the electrodes one by one and are electrically connected through wires, that is, the working pin 1111 corresponding to the working electrode 1131 is electrically connected through the wire 1121; the counter pin 1211 corresponding to the counter electrode 1231 is electrically connected through the wire 1221; and the reference pin 1311 corresponding to the reference electrode 1331 is electrically connected through the wire 1321. The wires are arranged on the surface of the substrate, and different pins, wires and electrodes are insulated from each other to prevent electrical signal crosstalk.

[0059] In the embodiment of the present invention, a temperature sensor 1431 (T) is also laid on the internal part Y, which is electrically connected to the pin on the external part X through a wire. It should be noted that two pins are provided on the external part X, which are electrically connected to the temperature sensor 1431 through two corresponding wires laid on the internal part Y. The temperature sensor and its wires and pins are also insulated from other electrodes and their pins and wires. In order to simplify the diagram, only one wire 1421 and one corresponding pin 1411 are shown in the figure, and only one wire and one corresponding pin are shown in other subsequent embodiments ( Figure 1e except).

[0060] In some embodiments of the present invention, the substrate 111 of the sensor 11 is generally a flexible material, such as a combination of one or more selected from polytetrafluoroethylene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polymethyl methacrylate, polycarbonate, and polyimide, all of which have good electrical insulation properties and can insulate electrodes and electrodes, electrodes and temperature sensors, and wires and wires disposed thereon from each other. In a preferred embodiment of the present invention, the substrate 111 is made of polyimide, which has good adaptability to human physiology and will not be subjected to excessive rejection reactions due to subcutaneous puncture.

[0061] The temperature sensor 1431 is a thin film thermistor. Preferably, the temperature sensor 1431 is a thin film platinum thermistor. An aluminum oxide layer is prepared as an insulating layer on the substrate 111 by a magnetron sputtering process or vacuum evaporation deposition method, a platinum film layer is prepared on the aluminum oxide layer by a magnetron sputtering process, and a wire is prepared by a magnetron sputtering process. Preferably, the wire is a metal alloy, and finally a liquid polyimide insulating layer is coated on the outer layer as a protective layer to reduce or eliminate the stress effect of different material layers, thereby obtaining a thin film platinum thermistor, wherein the protective layer avoids the central conductive area of ​​the temperature sensor 1431.

[0062] In other embodiments of the present invention, the thin film thermal resistor is a metal thin film thermal resistor, a carbon thin film resistor, a metal oxide thin film thermal resistor, or an alloy thin film thermal resistor.

[0063] In the embodiment of the present invention, Figure 1a As shown, the working electrode 1131 and the temperature sensor 1431 are located at the same depth of the subcutaneous tissue on the substrate 111, that is, the operating environment of the temperature sensor 1431 and the working electrode 1131 is the same. Therefore, the temperature measured by the temperature sensor 1431 is the operating temperature of the working electrode 1131, and there is no need to further compensate for the measured temperature, so that the blood sugar measurement value is more accurate. Figure 1a In the embodiment, the positions of the counter electrode 1231 and the reference electrode 1331 on the substrate 111 are also at the same depth of the internal body part, so that the area of ​​the internal body part Y is fully utilized to make the analyte sensor more miniaturized.

[0064] Since the analyte sensor itself is a miniaturized structure and its penetration depth under the skin is at the millimeter level, even if the temperature sensor 1431 and the working electrode 1131 are not at the same penetration depth under the skin, the depth difference is not large, and both are located under the skin. It can also be considered that the operating environment of the temperature sensor 1431 and the working electrode 1131 is the same, and the temperature measured by the temperature sensor 1431 is the operating temperature of the working electrode 1131. It can also be considered that the temperature measured by the temperature sensor 1431 is the patient's internal temperature. Therefore, in other embodiments of the present invention, the position arrangement relationship of the working electrode 1131, the counter electrode 1231, the reference electrode 1331 and the temperature sensor 1431 is not limited. For example, the working electrode 1131, the counter electrode 1231, the reference electrode 1331 and the temperature sensor 1431 can be arranged on the substrate in sequence from the proximal end to the distal end of the internal body part. It can be understood that the proximal end of the internal body part is the end close to the external body part X, and the distal end of the internal body part is the end away from the external body part X. Figure 1b As shown; the temperature sensor 1431 can also be at the same depth as the counter electrode 1231 or the reference electrode 1331; or other position arrangements, such as any two of the four components, the temperature sensor and the three electrodes, are located at one depth, and the other two are located at different depths, or any three of the four components are located at one depth, and the other is located at a different depth, etc., as long as the area of ​​the in vivo part Y is fully utilized while satisfying the analyte detection and temperature detection, but preferably, the working electrode 1131 and the temperature sensor 1431 are at the same depth of penetration into the subcutaneous tissue on the substrate 111.

[0065] exist Figure 1a In the embodiment, the conductor 1121 / 1221 / 1321 / 1421 is laid on the surface of the substrate 111. In other embodiments of the present invention, the conductor may also be arranged in the inner layer of the substrate, such as Figure 1bWhen the wire 1121 / 1221 / 1321 / 1421 is arranged in the inner layer of the substrate 111, and is electrically connected to the pins, electrodes, and temperature sensors arranged on the surface of the substrate 111, a hole 1141 / 1241 / 1341 / 1441 is opened at the corresponding position of the electrical connection on the substrate 111, and the electrical connection end of the wire 1121 / 1221 / 1321 / 1421 is led out to the surface of the substrate 111 through the hole 1141 / 1241 / 1341 / 1441, and is electrically connected to the electrode 1131 / 1231 / 1331 and the temperature sensor 1431 respectively. Similarly, the other end of the wire 1121 / 1221 / 1321 / 1421 is electrically connected to the pin 1111 / 1211 / 1311 / 1411 through the hole (not shown in the figure). When the wires 1121 / 1221 / 1321 / 1421 are arranged in the inner layer of the substrate 111, the substrate 111 can provide insulation protection for each wire to prevent short circuits between the wires and signal loss or instability, but the processing technology is relatively complicated.

[0066] The sensor 11 adopts a three-electrode system, including a working electrode, a counter electrode and a reference electrode, working pins, counter pins and reference pins corresponding to them, and wires connecting each pin and electrode. In other embodiments of the present invention, the sensor may also adopt a two-electrode system, which does not include a reference electrode and corresponding pins and wires. This is common knowledge in the art and will not be described in detail here.

[0067] like Figure 1c As shown, the substrate 111 is composed of four layers of substrates, each layer of substrate 111a / 111b / 111c / 111d can be provided with at least one electrode or temperature sensor, and each layer of substrate 111a / 111b / 111c / 111d can be provided with at least one wire in the inner layer. In other embodiments of the present invention, the wire can also be laid on the surface of the secondary substrate, such as Figure 1aAs shown. The electrodes 1131 / 1231 / 1331 and the temperature sensor 1431 are respectively arranged on different layers of sub-substrates 111a / 111b / 111c / 111d. On the one hand, the distance between the electrodes and between the electrodes and the temperature sensor can be increased, the signal interference between the electrodes and between the electrodes and the temperature sensor can be reduced, and the reliability of analyte detection and temperature detection can be improved; on the other hand, the electrodes or temperature sensors on each layer of the substrate can be arranged with a larger area. The electrodes or temperature sensors with a larger area can be in more complete contact with the body fluid, and the signals are more stable, thereby improving the reliability of analyte detection and temperature detection; on the third hand, since the electrodes or temperature sensors are arranged on different layers of sub-substrates, the wires 1121 / 1221 / 1321 / 1421 electrically connected to the electrodes or temperature sensors can also be routed on different sub-substrates, so the sub-substrates can also electrically insulate the wires 1121 / 1221 / 1321 / 1421. Based on this, the wires 1121 / 1221 / 1321 / 1 421 can be routed on the surface of each layer of substrate 111a / 111b / 111c / 111d, which simplifies the processing technology of the wire. Fourthly, although the wires 1121 / 1221 / 1321 / 1421 can be routed on the surface of different layers of sub-substrates 111a / 111b / 111c / 111d, once a certain layer of substrate is damaged, the wires of the adjacent two layers may contact and short-circuit. Therefore, it is necessary to lay the wires on the sub-substrates 111a / 111b / 111c / 111d. When 1121 / 1221 / 1321 / 1421 is used, the wires 1121 / 1221 / 1321 / 1421 can be staggered to form a stepped wire distribution. Even if a certain layer of the substrate is damaged, the wires of the two adjacent layers will not come into contact and short-circuit, thereby improving the reliability of analyte detection and temperature detection. Fifthly, the substrate composed of a combination of multiple layers of substrates has higher mechanical strength than that of a single-layer substrate, is not easily broken or damaged, and prolongs the service life of the analyte sensor.

[0068] In an embodiment of the present invention, the distribution of the three electrodes 1131 / 1231 / 1331 and the temperature sensor 1431 on each sub-substrate is not fixed, and can be randomly distributed on each level of the substrate, or arranged according to actual needs. For example, considering that the reference electrode 1331 is thicker than the working electrode and the counter electrode 1231, the reference electrode 1331 can be set on the bottom sub-substrate 111a to improve the thickness consistency of the sensor 11, so as to avoid excessive thickness difference in the sensor 11, thereby facilitating the storage and use of the sensor 11. Figure 1c The thickness of each layer of the sub-substrate 111a / 111b / 111c / 111d and the electrodes 1131 / 1231 / 1331 and the temperature sensor 1431 are expressed in an exaggerated form. It can be understood that this does not affect the description of the present solution.

[0069] In some embodiments of the present invention, each layer of the sub-base can be prepared layer by layer, that is, after preparing the bottom layer base 111a, the third layer base 111b is prepared on the basis of the bottom layer base 111a. Similarly, after preparing the third layer base 111b, the second layer base 111c is prepared. After preparing the second layer base 111c, the top layer base 111d is prepared. In the usual preparation process, when preparing each layer of the base, the base material, such as polyimide, is heated and coated on the mold layer by layer, and a complete sub-base is formed after curing. However, during the curing process, the material in some areas may not be sufficiently cured, or the curing degree of the base material at various locations on the sub-base is inconsistent, or the curing degree of the base material on different layers of the sub-base is inconsistent, resulting in brittle cracking of the base during subsequent use, which may cause the electrodes, wires, and pins arranged on the base to short-circuit with each other, or even be damaged, affecting the detection reliability of the sensor.

[0070] Based on the existing problem that the substrate may fail due to brittle cracking, in other embodiments of the present invention, the sub-substrates 111a / 111b / 111c / 111d of each layer may be prefabricated first. Here, prefabrication means that the substrate material of each layer of the substrate 111a / 111b / 111c / 111d is fully solidified, and then electrodes / temperature sensors, wires or pins are processed on the substrate. According to the design requirements of the sensor, the electrodes, wires or pins set on each layer of the substrate may be the same or different. After the sub-substrates 111a / 111b / 111c / 111d of each layer are prefabricated, they are combined into a whole by pasting. For example, when the material of the sub-substrates 111a / 111b / 111c / 111d is polyimide, the precursor of polyimide can be used to paste the substrates 111a / 111b / 111c / 111d of each layer to finally obtain a complete sensor substrate. Since the substrates 111a / 111b / 111c / 111d of each layer are pasted together after being fully cured, the brittle cracking problem caused by insufficient curing of the materials in the same layer of substrates and the brittle cracking problem caused by insufficient curing of the materials between the sub-substrates of different layers can be avoided, thereby improving the detection reliability of the sensor. In addition, since the substrates 111a / 111b / 111c / 111d of each layer can be prefabricated independently and then assembled into a whole, the manufacturing efficiency of the sensor can also be increased in the manufacturing process.

[0071] It is worth pointing out that in some embodiments of the present invention, on the top layer of the secondary substrate 111d, pins 1111 / 1211 / 1311 / 1411 corresponding to the various electrodes and temperature sensors 1131 / 1231 / 1331 / 1431 need to be prefabricated to complete the functions of the sensor 11. After the secondary substrates 111a / 111b / 111c / 111d of each layer are pasted, the wires on the secondary substrates 111b / 111c / 111d are led to the top layer of the secondary substrate 111a by punching holes to establish electrical connection with the pins on the secondary substrate 111a.

[0072] In some embodiments of the present invention, the thickness of each layer of the substrate 111a / 111b / 111c / 111d may be 0.1-100 um. Figure 1a and 1b In the scheme of the single-layer substrate shown, the thickness of each layer of the substrate 111a / 111b / 111c / 111d is thinner, otherwise the thickness of several layers of the substrate is too thick, and there is not enough softness, which will increase the user's discomfort when piercing the user's subcutaneous tissue. Therefore, preferably, the thickness of each layer of the substrate 111a / 111b / 111c / 111d is 0.1-20um, and further preferably, the thickness of each layer of the substrate 111a / 111b / 111c / 111d is about 10um, and the thickness after forming the whole is about 25-35um. This thickness will not be easily damaged or broken due to being too thin, nor will it increase the user's discomfort due to being too thick. It can be understood by those skilled in the art that due to the error of the processing technology, the actual thickness of each layer of the secondary substrate 111a / 111b / 111c / 111d may have deviations.

[0073] In some embodiments of the present invention, the material of each layer of substrate 111a / 111b / 111c / 111d is preferably polyimide. In order to stick the various layers of substrate 111a / 111b / 111c / 111d into a whole, the pasting material may preferably be a polyimide precursor. After the polyimide precursor is cured, it can maintain consistency in physical properties with polyimide. Such pasting method can prevent the various layers of substrate 111a / 111b / 111c / 111d from peeling off or even falling off due to stress concentration or uneven stress.

[0074] exist Figure 1d In the embodiment, the substrate 111 is composed of two layers of substrates 111e and 111f. The working electrode 1131 and the temperature sensor 1431 are arranged in parallel on the sub-substrate 111e. The inner layer of the sub-substrate 111e is also provided with wires 1121 and 1421. In other embodiments of the present invention, the wires can also be laid on the surface of the sub-substrate, such as Figure 1aThe counter electrode 1231 and the reference electrode 1331 are arranged in parallel on the secondary substrate 111f, and the inner layer of the secondary substrate 111f is also provided with wires 1221 and 1321. In other embodiments of the present invention, the wires can also be laid on the surface of the secondary substrate, such as Figure 1a As shown. Using two layers of substrate, it can have both Figure 1c The advantages of the multi-layer substrate described in the embodiment of the present invention are to improve the reliability of analyte detection and temperature detection, and extend the service life of the analyte sensor. At the same time, the working electrode and the temperature sensor are at the same depth of penetration into the subcutaneous tissue, so that the operating environment of the temperature sensor and the working electrode is the same. Therefore, the temperature measured by the temperature sensor is the operating temperature of the working electrode, and there is no need to further compensate the measured temperature, so that the blood glucose measurement value is more accurate. Furthermore, the counter electrode and the reference electrode are arranged on the same sub-substrate, which fully utilizes the area of ​​the inner part Y of the sub-substrate 111f, and at the same time makes the analyte sensor a miniaturized structure.

[0075] As mentioned above, since the analyte sensor itself is a miniaturized structure and its penetration depth under the skin is at the millimeter level, even if the temperature sensor and the working electrode are not at the same penetration depth under the skin, the depth difference is not large, and both are located under the skin. It can also be considered that the operating environment of the temperature sensor and the working electrode is the same, and the temperature measured by the temperature sensor is the operating temperature of the working electrode. Therefore, in other embodiments of the present invention, the position arrangement relationship of the working electrode, the counter electrode, the reference electrode and the temperature sensor is not limited. For example, the temperature sensor and the reference electrode or the counter electrode are located on the same primary substrate, while the other two electrodes are located on the same primary substrate; or only one of the four components of the three electrodes and the temperature sensor is arranged on a certain primary substrate, and the other three are arranged on another secondary substrate. Users can set it according to actual needs, and the corresponding wires can be arranged on the surface or inner layer of the corresponding secondary substrate.

[0076] In another embodiment of the present invention, the sensor may also include a three-layer substrate, any two of the four components, namely, the three electrodes and the temperature sensor, may be arranged on the same level of substrate, while the other two may be separately arranged on the other two levels of substrates, and the four components may be arranged on the same surface of all sub-substrates, such as surface A, and their corresponding wires may be arranged on the surface or inner layer of the corresponding sub-substrate.

[0077] Generally, the working electrode and the counter electrode are selected from one of the materials such as graphite electrode, glassy carbon electrode, noble metal, etc., and the reference electrode is selected from one of the materials such as Ag / AgCl or calomel. Considering the requirements of good ductility and surface structure stability, noble metal electrodes such as gold electrodes, platinum electrodes, silver electrodes, etc. become better choices. Preferably, the working electrode and the counter electrode are both platinum electrodes. In the embodiment of the present invention, the temperature sensor is preferably a thin film platinum thermistor. Therefore, the temperature sensor can also be embedded in the working electrode or the counter electrode. In addition to realizing the functions of analyte detection and temperature detection at the same time, one electrode can be reduced to make the processing simpler. Figure 1e As shown, the temperature sensor 1431 is embedded in the counter electrode 1231, and the temperature sensor 1431 is a thin film platinum thermal resistor strip, one end of which is connected to the temperature sensor dedicated pin through a wire, and the other end is connected to the common pin of the temperature sensor and the counter electrode through a wire. Therefore, the function of analyte detection can be realized through the pin of the working electrode, the common pin of the counter electrode and the temperature sensor, and the pin of the reference electrode, while temperature detection can be realized through the common pin of the temperature sensor and the counter electrode and the dedicated pin of the temperature sensor. In the embodiment of the present invention, the resistor strip can increase the length of the resistor strip by reciprocating arrangement, thereby increasing the resistance of the resistor strip, and better realizing analyte detection and temperature detection.

[0078] In other embodiments of the present invention, when the sensor is a dual-electrode system, that is, the sensor only includes a working electrode and a counter electrode, when the temperature sensor can also be embedded in the working electrode or the counter electrode, one electrode can be reduced to further simplify the process. Preferably, the temperature sensor is embedded in the counter electrode.

[0079] Embodiment 2

[0080] Figure 2a-2k Schematic diagram of an analyte sensor in which at least one electrode and a temperature sensor are located on different surfaces of a substrate according to an embodiment of the present invention.

[0081] The sensor is a planar structure, therefore, there are two opposite surfaces, namely surface A and surface B. When the three electrodes and the temperature sensor are arranged on the surface A and surface B of the substrate, the surface A and surface B of the substrate can be fully utilized, and the electrodes and temperature sensors can be set to a larger area. Electrodes with larger areas are in more complete contact with body fluids, and the signals are more stable, thereby improving the reliability of analyte detection. On the one hand, temperature sensors with larger areas have greater resistance, making temperature measurement more sensitive. On the other hand, they are in more complete contact with body fluids, and the signals are more stable, thereby improving the reliability of temperature detection. The four components of the three electrodes and the temperature sensor can be arranged on the surface A and surface B of the substrate in any form, such as arranging three components on one side and one component on the other side; or arranging two components on each side. Preferably, the working electrode and the temperature sensor are arranged on both sides of the substrate and are at the same depth of penetration into the subcutaneous tissue. The temperature measured by the temperature sensor is the operating temperature of the working electrode, and there is no need to further compensate for the measured temperature, so that the blood glucose measurement value is more accurate. Figure 2a and 2b As shown, the reference electrode and the counter electrode can be arranged on one side of the substrate or on both sides of the substrate according to actual needs. The arrangement can be parallel to the working electrode or the temperature sensor (such as Figure 1a ) or in order (such as Figure 1b ), the wires can also be arranged on the surface of the substrate (such as Figure 1a ) or inner layer (such as Figure 1b ).

[0082] exist Figure 2a In the embodiment, the sensor 21 includes only one layer of substrate 211, the working electrode 2131, the counter electrode 2231 and the reference electrode 2331 are arranged on the A side, and the corresponding pins are also arranged on the A side; the temperature sensor 2431 is arranged on the B side, and the corresponding pins are also arranged on the B side, and the temperature sensor 2431 and the working electrode 2131 are at the same depth of penetration into the subcutaneous tissue. The wires 2121 / 2221 / 2321 / 2421 are laid on the surfaces of the A side and the B side. As mentioned above, the wires 2121 / 2221 / 2321 / 2421 can also be arranged in the inner layer of the A side and the B side. When there are substrates on both sides of the substrate and the sensor is inserted into the subcutaneous tissue in a bending manner, it needs to be installed in the analyte detection device in the form of a three-dimensional circuit. The specific technical solution can refer to the disclosed patent PCT / CN2022 / 080845.

[0083] When the temperature sensor 2431 is located alone on one side of the substrate, the three-electrode system and the temperature sensor can be prepared separately during manufacturing, thereby improving the yield of the finished product. At the same time, the analyte detection signal of the three-electrode system and the temperature detection signal of the temperature sensor do not interfere with each other, thereby improving the accuracy of analyte detection and temperature detection.

[0084] exist Figure 2bIn the embodiment, the sensor 21 includes only one layer of substrate 211, the working electrode 2131 and the reference electrode 2331 are arranged on the A surface, and the corresponding pins are also arranged on the A surface; the temperature sensor 2431 and the counter electrode 2231 are arranged on the B surface, and the corresponding pins are also arranged on the B surface, and the temperature sensor 2431 and the working electrode 2131 are at the same depth of penetration into the subcutaneous tissue. The wires 2121 / 2221 / 2321 / 2421 are laid on the surface of the A surface and the B surface. As mentioned above, the wires 2121 / 2221 / 2321 / 2421 are laid on the inner layer of the A surface and the B surface. The counter electrode 2231 and the temperature sensor 2431 are arranged on the same surface of the substrate. On the one hand, a structure in which the temperature sensor 2431 is embedded in the counter electrode 2231 can be selected to make the area of ​​the temperature sensor 2431 larger. As mentioned above, the sensitivity and accuracy of temperature detection can be improved. On the other hand, the relative distance between the counter electrode 2231 and the working electrode 2131 can be increased, and the current crosstalk between the counter electrode 2231 and the working electrode 2131 can be reduced, thereby reducing noise. At the same time, the area of ​​the counter electrode 2231 can be maximized, thereby reducing electrochemical polarization and improving the accuracy and sensitivity of the analyte detection signal.

[0085] In other embodiments of the present invention, the reference electrode 2331 and the temperature sensor 2431 can also be arranged on the same side of the substrate. In this case, on the one hand, the circuit risk caused by the migration of Ag / Cl substances in the reference electrode 2331 can be reduced, thereby improving the reliability of analyte detection. On the other hand, when the reference electrode 2331 fails, the three-electrode system becomes a two-electrode system and can still be used normally, thereby improving the stability of analyte detection.

[0086] Figure 2c-2k The analyte sensor with integrated temperature sensor includes a multi-layer substrate. The benefits of using the multi-layer substrate are as described above and will not be repeated here.

[0087] exist Figure 2c-2f The sensor in the embodiment includes two layers of substrates 211a and 211b, three electrodes and a temperature sensor. Among these four components, at least one electrode and the temperature sensor are arranged on different surfaces of the sub-substrate. Figure 2c and 2d As shown, in Figure 2cIn the embodiment, the A surface of the sub-base 211a and the B surface of the sub-base 211b are respectively provided with three electrodes and two of the four components of the temperature sensor, that is, the temperature sensor 2431 and the two electrodes are provided on different surfaces of the sub-base. The arrangement of these four components is not limited in the embodiment of the present invention. Preferably, the working electrode 2131 and the temperature sensor 2431 are arranged on different surfaces at the same depth of penetration under the skin, so that the operating environment of the temperature sensor and the working electrode is the same. Therefore, the temperature measured by the temperature sensor is the operating temperature of the working electrode, and there is no need to further compensate the measured temperature, so that the blood sugar measurement value is more accurate. Figure 2c As shown, the reference electrode 2331 and the working electrode 2131 are sequentially arranged on the secondary substrate 211a, and the counter electrode 2231 and the temperature sensor 2431 are sequentially arranged on the secondary substrate 211b. In other embodiments of the invention, the reference electrode 2331 and the working electrode 2131 can also be arranged in parallel on the secondary substrate 211a (such as Figure 1a ), the electrode 2231 and the temperature sensor 2431 are arranged in parallel on the sub-base 211b (such as Figure 1a ), the wires 2121 / 2221 / 2321 / 2421 can be laid on the surface or inner layer of the secondary substrate.

[0088] exist Figure 2d In the embodiment of the present invention, the temperature sensor 2431 and the reference electrode 2231 are both arranged on the B surface of the sub-base 211b, but the working electrode 2131 and the counter electrode 2331 are respectively arranged on the A surface of the sub-bases 211a and 211b, and the wires 2121 / 2221 / 2321 / 2421 can be laid on the surface or inner layer of the sub-base. In the embodiment of the present invention, it is not limited which two of the four components of the three electrodes and the temperature sensor are arranged on one side, nor is it limited how the two components are arranged on the surface of the sub-base. Preferably, the working electrode 2131 and the temperature sensor 2431 are arranged on different sides at the same depth of penetration under the skin, so that the operating environment of the temperature sensor and the working electrode is the same. Therefore, the temperature measured by the temperature sensor is the operating temperature of the working electrode, and there is no need to further compensate the measured temperature, so that the blood glucose measurement value is more accurate.

[0089] exist Figure 2e-2gIn the embodiment, the sensor includes two layers of substrates 211a and 211b, one of the three electrodes and the temperature sensor is arranged on one side of a sub-substrate, such as the B side, and the other three are arranged on the other side of the sub-substrate, such as the A side, including the A side of the sub-substrates 211a and 211b. In the embodiment of the present invention, it is not limited which of the three electrodes and the temperature sensor is arranged on one side, nor is it limited how the other three components are arranged on the other side of the sub-substrates 211a and 211b. Preferably, the working electrode 2131 and the temperature sensor 2431 are arranged on different sides at the same depth of penetration under the skin, so that the operating environment of the temperature sensor and the working electrode is the same. Therefore, the temperature measured by the temperature sensor is the operating temperature of the working electrode, and there is no need to further compensate the measured temperature, so that the blood glucose measurement value is more accurate.

[0090] exist Figure 2e In the embodiment, the temperature sensor 2431 is arranged on the B surface of the secondary substrate 211b, the working electrode 2131, the counter electrode 2231 and the reference electrode 2331 are arranged on the A surface of the secondary substrate 211a, and the corresponding pins are arranged on the same surface as the electrodes and the temperature sensor. The wire can be arranged on the surface or inner layer of the secondary substrate. When the temperature sensor 2431 is located alone on one side of the substrate, the three-electrode system and the temperature sensor can be prepared separately on the secondary substrates 211a and 211b during manufacturing, thereby improving the yield of the finished product. At the same time, the analyte detection signal of the three-electrode system and the temperature detection signal of the temperature sensor do not interfere with each other, thereby improving the accuracy of analyte detection and temperature detection. At this time, the temperature sensor and the three electrodes are arranged on different surfaces of the substrate. When the temperature sensor is exchanged with any one of the three electrodes, the temperature sensor and one electrode are arranged on different surfaces of the substrate.

[0091] exist Figure 2f In the embodiment, the temperature sensor 2431 is arranged on the B surface of the sub-substrate 211b, and the working electrode 2131 and the counter electrode 2231 are arranged in sequence on the A surface of the sub-substrate 211b. Of course, the working electrode 2131 and the counter electrode 2231 can also be arranged in parallel on the A surface of the sub-substrate 211b, and the reference electrode 2331 is arranged on the A surface of the sub-substrate 211a. In other embodiments of the invention, the working electrode 2131 and the reference electrode 2331 can also be arranged in sequence or in parallel on the A surface of the sub-substrate 211b, while the counter electrode 2231 is arranged alone on the A surface of the sub-substrate 211a; the working electrode 2131 can also be arranged alone on the A surface of the sub-substrate 211b, while the counter electrode 2231 and the reference electrode 2331 are arranged in sequence or in parallel on the A surface of the sub-substrate 211a, as shown in FIG. Figure 2g shown.

[0092] exist Figure 2h-2jIn the embodiment, the sensor includes three layers of substrates 211a, 211b and 211c, one of the four components of three electrodes and temperature sensor is arranged on one side of a sub-substrate, such as side B, and the other three are arranged on the other side of the sub-substrate, such as side A, including side A of sub-substrates 211a, 211b and 211c. In the embodiment of the present invention, it is not limited which of the four components of three electrodes and temperature sensor is arranged on one side, nor is it limited how the other three components are arranged on the other side of the sub-substrates 211a, 211b and 211c. Preferably, the working electrode 2131 and the temperature sensor 2431 are arranged on different sides at the same depth of penetration under the skin, so that the operating environment of the temperature sensor and the working electrode is the same. Therefore, the temperature measured by the temperature sensor is the operating temperature of the working electrode, and there is no need to further compensate the measured temperature, so that the blood glucose measurement value is more accurate.

[0093] exist Figure 2h In the figure, the temperature sensor 2431 is arranged on the B surface of the sub-base 211c, and its pins are also arranged on the B surface of the sub-base 211c. The other three electrodes are arranged on the A surfaces of the three sub-bases respectively, and their pins are all arranged on the A surface of the sub-base 211a. The wires can be optionally arranged on the surface or inner layer of the sub-base.

[0094] exist Figure 2i In the figure, the temperature sensor 2431 is arranged on the B surface of the sub-substrate 211c, and its pins are also arranged on the B surface of the sub-substrate 211c. The working electrode 2131 and the counter electrode 2231 are arranged in sequence on the A surface of the sub-substrate 211b. Of course, the working electrode 2131 and the counter electrode 2231 can also be arranged in parallel on the A surface of the sub-substrate 211b, and the reference electrode is individually arranged on the A surface of the sub-substrate 211a. The pins of the three electrodes are all arranged on the A surface of the sub-substrate 211a, and the wires can be selectively arranged on the surface or inner layer of the sub-substrate; in other embodiments of the invention, the reference electrode and the working electrode can also be arranged in sequence or in parallel on the A surface of the sub-substrate 211b, and the counter electrode can be individually arranged on the A surface of 211a; or the working electrode can be individually arranged on the A surface of the sub-substrate 211b, and the reference electrode and the counter electrode can be arranged in sequence or in parallel on the A surface of the sub-substrate 211a, and the wires can be selectively arranged on the surface or inner layer of the sub-substrate.

[0095] Figure 2j and Figure 2i The difference is that the working electrode 2131 is arranged on the A surface of the sub-substrate 211a, the reference electrode 2331 and the counter electrode 2231 are arranged on the A surface of the sub-substrate 211b, and the temperature sensor 2431 is still arranged on the B surface of the sub-substrate 211c. The temperature sensor 2431 and the working electrode 2131 are also at the same depth of penetration under the skin. At this time, the temperature sensor 2431 and the working electrode 2131 are on different surfaces of the spaced sub-substrate.

[0096] In another embodiment of the present invention, the sensor includes 4 layers of substrates, one of the 4 components, the three electrodes and the temperature sensor, is arranged on one side of a secondary substrate, and the other three components are arranged on the other side of the other three layers of substrates. In the embodiment of the present invention, the arrangement of the 4 components on the 4 layers of substrates is not limited. Preferably, the working electrode 2131 and the temperature sensor 2431 are arranged on different sides at the same depth of penetration under the skin, so that the operating environment of the temperature sensor and the working electrode is the same. Therefore, the temperature measured by the temperature sensor is the operating temperature of the working electrode, and there is no need to further compensate the measured temperature, so that the blood glucose measurement value is more accurate. As in Figure 2k In the figure, the temperature sensor 2431 is arranged on the B surface of the sub-substrate 211d, and its pins are also arranged on the B surface of the sub-substrate 211d. The working electrode is arranged on the A surface of the sub-substrate 211c, and is at the same depth of penetration into the skin as the temperature sensor 2431. The reference electrode 2331 and the counter electrode 2231 are respectively arranged on the A surfaces of the sub-substrates 211a and 211b, and the pins of the three electrodes are all arranged on the A surface of the sub-substrate 211a. The wires can be optionally arranged on the surface or inner layer of the sub-substrate.

[0097] In various embodiments of the present invention, the counter electrode or the working electrode may be selectively embedded according to the arrangement of the electrodes and the temperature sensor on each substrate.

[0098] Embodiment 3

[0099] Figure 3a-3f Schematic diagram of an analyte sensor with an integrated temperature sensor having an insulating material disposed thereafter in an embodiment of the present invention.

[0100] In some embodiments of the present invention, after the sensor is inserted into the subcutaneous tissue, in order to adapt to the repeated peristalsis of the muscle, the base is generally soft. However, the soft base is repeatedly bent or folded during the repeated peristalsis of the muscle, and the base is prone to prematurely reach the limit fatigue (not reaching the designed service life of the sensor, such as 14 days), resulting in damage or even breakage, which will expose the electrodes, temperature sensors or wires arranged on the base and short-circuit, or directly break and damage, affecting the reliability of the sensor's analyte detection and temperature detection. In order to improve the reliability of the sensor's analyte detection and temperature detection, the mechanical strength of the base needs to be strengthened to extend the time for the base to reach the limit fatigue and meet the designed service life of the sensor.

[0101] In some embodiments of the present invention, insulating materials for strengthening the mechanical strength of the substrate may be disposed in some areas of the substrate. Here, "later disposed" means that after the sensor is processed, that is, after the electrodes, temperature sensors, pins and wires are disposed on the substrate to form a complete sensor, at least one layer of insulating material is disposed on the substrate. Obviously, after the insulating material is added, the mechanical strength of the substrate in the corresponding area will be improved, and the time to reach the ultimate stress fatigue will also be extended.

[0102] In some embodiments of the present invention, the number of layers of insulating material disposed on the substrate may be multiple layers, such as 2 layers, 3 layers or more layers, which can further increase the mechanical strength of the substrate. However, after multiple layers of insulating material are disposed, the substrate in the corresponding area will become stiff, which will increase the user's discomfort after piercing the subcutaneous tissue. Similarly, the thicker the insulating material is, the greater the mechanical strength of the substrate can be. However, too thick an insulating material will also cause the substrate in the corresponding area to become stiff, which will increase the user's discomfort after piercing the subcutaneous tissue. Therefore, it is necessary to control the number of layers and thickness of the insulating material.

[0103] In a preferred embodiment of the present invention, the number of layers of the insulating material is 1 to 10, and the thickness of each layer is 0.1 um to 100 um.

[0104] In a preferred embodiment of the present invention, the number of layers of insulating material is 1, and the thickness is 25um. During the sensor processing, providing multiple layers of insulating material will increase the complexity of the processing. Therefore, providing 1 layer of insulating material can both enhance the mechanical strength of the substrate and will not lead to an overly complicated processing process. The thickness is set to 25um so that the substrate can maintain sufficient softness and will not increase the user's discomfort after the substrate penetrates the user's subcutaneous tissue.

[0105] In some embodiments of the present invention, the material of the insulating material can be a combination of one or more of polytetrafluoroethylene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polymethyl methacrylate, polycarbonate, and polyimide. The characteristics of the above materials have been described above and will not be repeated here. Preferably, the material of the insulating material is polyimide, which is consistent with the material of the substrate and has the same physical properties. When the actions of extension, contraction, bending, etc. occur, the insulating material and the substrate of the same material have the same extension, contraction or bending scale, and the insulating material will not be wrinkled or fall off due to stress concentration on the substrate due to different scales.

[0106] In some embodiments of the present invention, the insulating material may be disposed on the substrate by coating. When the insulating material is made of polyimide, the polyimide may be first heated to a liquid state and then coated on the substrate.

[0107] In other embodiments of the present invention, the insulating material can be set on the substrate by pasting. When the insulating material is made of polyimide, a polyimide precursor can be used as an adhesive material. After the polyimide precursor is cured, its physical properties are basically consistent with those of polyimide, and it is consistent when stretched, contracted, and bent. The insulating material will not bulge, wrinkle, or fall off on the substrate due to stress concentration or uneven stress, thereby improving the finished product yield of the sensor.

[0108] In the above-mentioned process of setting the insulating material on the substrate by coating or pasting, it is necessary to first ensure that the electrodes, temperature sensors, pins and wires on the substrate establish good electrical connections, and that there is good insulation between the electrodes, temperature sensors and electrodes, pins and pins, and wires and wires, so that the sensor function can be effectively realized.

[0109] In some embodiments of the present invention, when the insulating material is later disposed on the substrate, it should avoid the area where the pins and the electrode / temperature sensor are located, otherwise the sensor function will not be realized. Therefore, the area where the insulating material is later disposed includes at least one of the pin reverse area 312 of the pin area a or the electrode / temperature sensor reverse area 313 of the electrode / temperature sensor area b. Preferably, the insulating material is disposed on both the pin reverse area 312 and the electrode / temperature sensor reverse area 313.

[0110] In other embodiments of the present invention, the area where the insulating material is later set may also include the area near the electrode / temperature sensor and the pin, avoiding the central conductive area of ​​the electrode / temperature sensor and the pin. In this case, the insulating material can cover the edges of the electrode / temperature sensor and the pin, increase the adhesion between the electrode / temperature sensor and the pin and the substrate, prevent the edges of the electrode / temperature sensor and the pin from warping, and further prevent the electrode / temperature sensor and the pin from being damaged or even falling off.

[0111] In some embodiments of the present invention, the pin back area 312 and the electrode / temperature sensor back area 313 may be as follows: Figure 3a-3f As shown in FIG. 1 , the pin back side region 312 and the electrode / temperature sensor back side region 313 may be connected to form a continuous region in other embodiments of the present invention.

[0112] In other embodiments of the present invention, the sensor 31 may be installed in the analyte detection device in a bent form, that is, the external part X is bent or curved relative to the internal part Y, or the internal part Y is bent or curved relative to the external part X. Since the external part X is fixed in the analyte detection device, and the external part Y is inserted into the subcutaneous tissue and moves with the muscle peristalsis of the user, the internal part Y is often bent or curved relative to the external part X, and it is also necessary to set an insulating material behind the bent front area 314 of the internal part Y relative to the bending area c of the external part X. On the one hand, setting the insulating material behind the bent front area 314 can increase the mechanical strength of the substrate of the corresponding area, and on the other hand, when the wire is set on the surface of the substrate, it can also cover the wire of the corresponding area and provide additional insulation and protection for the wire.

[0113] It should be noted that, in the embodiment of the present invention, in order to make full use of the area of ​​the substrate, the working electrode, the reference electrode, the counter electrode and the temperature sensor are closely arranged in the internal part Y of the substrate within a safe distance. Therefore, under normal circumstances, the internal part Y does not need to be provided with insulating materials. However, due to other possible reasons, such as the presence of special-shaped electrodes or temperature sensors, there is a large gap between the three electrodes and the temperature sensor, or between these four components and the edge of the substrate. Insulating materials can be provided in the gap area to increase the mechanical strength of the corresponding area, such as Figure 3a and Figure 3e As shown in Figure 315.

[0114] In the embodiment of the present invention, according to the number of layers of sensors, the arrangement of electrodes or temperature sensors on the substrate, an insulating material can be disposed later, such as in Figure 3a In the embodiment, the sensor includes a single-layer substrate, the electrodes and the temperature sensor are arranged side by side on the substrate, and insulating materials can be disposed in the pin back area 312, the electrode / temperature sensor back area 313, the bent front area 314 and / or the area 315 with a large spacing on the body part Y. Figure 3b In the embodiment, the sensor includes a single-layer substrate, and the electrodes and the temperature sensor are arranged in sequence on the substrate. Insulating materials may be disposed in the pin back area 312, the electrode / temperature sensor back area 313 and / or the bent front area 314.

[0115] exist Figure 3cIn the embodiment, the sensor includes a multi-layer substrate, specifically, a 4-layer substrate, and the three electrodes and the temperature sensor are arranged on the 4-layer substrate respectively. The pin reverse area 312, the electrode reverse area 313 and / or the bent front area 314 of the A surface of the uppermost layer 311d on the B surface of the lowermost layer of the secondary substrate 311a can be provided with insulating materials. When the sensor includes other multi-layer substrates, and the temperature sensor and the three electrodes are provided on the same side of all the secondary substrates at the same time, such as the two-layer or three-layer substrate described in the first embodiment, similarly, the pin reverse area 312, the electrode / temperature sensor reverse area 313 and / or the bent front area 314 of the A surface of the uppermost layer on the B surface of the lowermost layer of the secondary substrate can be provided with insulating materials, and if there are large intervals between the two surfaces of the secondary substrate, insulating materials can be provided to increase the mechanical strength of the substrate.

[0116] exist Figure 3d-3e In the figure, the sensor includes a single-layer substrate, three electrodes and a temperature sensor are arranged on both sides of the substrate, and insulating materials can be arranged on the bent front area 314 of the substrate A side, the electrode back area 313 on the substrate B side and / or the areas 315 with larger intervals on both sides of the substrate to increase the mechanical strength of the substrate.

[0117] exist Figure 3f In the embodiment, the sensor includes a multi-layer substrate, specifically, a 4-layer substrate, the surfaces of the top and bottom substrates are provided with pins, the electrodes and the temperature sensor are arranged on different surfaces of the 4-layer substrate, and the electrode back surface area 313 on the B surface of the bottom layer of the secondary substrate 311a and / or the bent front surface area 314 of the A surface of the top layer 311d can be provided with insulating materials. When the sensor includes other multi-layer substrates, and the temperature sensor and at least one electrode are provided on different surfaces of all the secondary substrates, such as the two-layer or three-layer substrate described in the second embodiment, similarly, the electrode / temperature sensor back surface area 313 on the B surface of the bottom layer of the secondary substrate and / or the bent front surface area 314 of the A surface of the top layer can be provided with insulating materials, and if there are large intervals between the two surfaces of the secondary substrate, insulating materials can be provided to increase the mechanical strength of the substrate.

[0118] In various embodiments of the present invention, the counter electrode or the working electrode may be selectively embedded according to the arrangement of the electrodes and the temperature sensor on each substrate.

[0119] Example 4

[0120] Figures 4a-4f Schematic diagram of an analyte sensor of an integrated temperature sensor provided with a protective layer according to an embodiment of the present invention.

[0121] In some embodiments of the present invention, after the electrodes, temperature sensors, wires and pins are manufactured on the substrate, a protective layer 416 may be provided on the substrate. The protective layer 416 may cover the entire substrate or a certain area of ​​the substrate, but expose the central area of ​​the pins, electrodes and temperature sensors and cover the edges of the pins, electrodes and temperature sensors. Firstly, the protective layer 416 can enhance the mechanical strength of the substrate and prolong the time before the substrate is damaged; secondly, the protective layer 416 covers the edges of the pins, electrodes and temperature sensors to prevent irregular edges from being exposed and causing signal noise, thereby improving the stability of the detection signal; thirdly, the electronic conduction layer of the electrode is fixed on the substrate. Since the substrate is repeatedly bent during use, the metal film of the electronic conduction layer will inevitably separate from the substrate and cause warping, bubbling or even falling off. After the protective layer 416 is provided, the protective layer 416 can also enhance the adhesion between the metal film of the electronic conduction layer and the substrate, thereby avoiding warping and bubbling of the metal film and improving the reliability of the sensor's analyte detection; the aluminum oxide insulating layer of the temperature sensor is also provided on the substrate. Since the substrate is repeatedly bent during use, warping, bubbling or even falling off may also occur. After the protective layer 416 is provided, the protective layer 416 can also enhance the adhesion between the aluminum oxide insulating layer and the substrate, thereby avoiding warping and bubbling of the insulating layer and improving the reliability of the sensor's temperature detection.

[0122] In an embodiment of the present invention, a corresponding protective layer 416 may be provided according to the number of layers of the sensor substrate or sub-substrate and the arrangement of electrodes or temperature sensors on the substrate. Specifically, as long as pins, electrodes or temperature sensors are provided on a certain surface of a certain layer of the substrate or sub-substrate, a protective layer 416 may be provided on that surface, but the central area of ​​the pins, electrodes and / or temperature sensors needs to be exposed and the edges of the pins, electrodes and / or temperature sensors need to be covered.

[0123] As in Figure 4a and 4b In the embodiment, the sensor includes a substrate 411, a working electrode 4131, a counter electrode 4231, a reference electrode 4331 and a temperature sensor 4431 are arranged in parallel or in sequence on the A surface of the substrate 411. Therefore, a protective layer is only provided on the A surface of the substrate 411, exposing the central area of ​​the pins, electrodes and the temperature sensor and at least covering the edges of the pins, electrodes and the temperature sensor.

[0124] exist Figure 4cIn the embodiment, the sensor includes 4 layers of substrates, and the electrodes and the temperature sensor are respectively arranged on the same surface of the 4 layers of substrates, such as surface A. Therefore, a protective layer 416 is arranged on surface A of each layer of substrate, exposing the central area of ​​the pins, electrodes and temperature sensors and at least covering the edges of the pins, electrodes and temperature sensors. When the sensor includes 2 or 3 layers of substrates, and the electrodes and the temperature sensor are respectively arranged on the same surface of different layers of substrates, such as the two or three layers of substrates described in the first embodiment, a protective layer can also be arranged on the corresponding surface.

[0125] exist Figure 4d and 4e In the process, the electrodes and the temperature sensor are arranged on different surfaces of the substrate. Figure 4d and 4e The substrate 411 is a single-layer substrate, and electrodes and / or temperature sensors are arranged on both sides of the substrate 411. Therefore, protective layers 416 are arranged on both sides of the substrate 411 to expose the central area of ​​the pins, electrodes and / or temperature sensors and cover the edges of the pins, electrodes and / or temperature sensors.

[0126] Figure 4f In the embodiment, the sensor includes a multi-layer substrate, specifically, a 4-layer substrate, the electrodes and the temperature sensor are respectively arranged on different surfaces of different sub-substrates, and the surface where the electrode / temperature sensor is arranged is correspondingly provided with a protective layer 416, while exposing the central area of ​​the pins, electrodes and temperature sensors and at least covering the edges of the pins, electrodes and temperature sensors. When the sensor includes a 2-layer or 3-layer substrate, at least one electrode and a temperature sensor are respectively arranged on different surfaces of the sub-substrate, such as the two-layer or three-layer substrate described in the second embodiment, a protective layer can also be provided on the corresponding surface.

[0127] In some embodiments of the present invention, in order to reduce the manufacturing process and difficulty of the sensor and save material costs, for the sensor, the electrodes and temperature sensors are more valuable than the pins and are sensitive components. It can be given priority to set the protective layer 416 to cover the edges of the electrodes and / or temperature sensors, that is, the protective layer 416 does not cover the entire substrate, but covers a part of the substrate.

[0128] In some embodiments of the present invention, the protective layer 416 has a thickness thicker than the electrode and the temperature sensor, for example, 1 to 25 um. After the protective layer 416 is applied, a pit is formed at the location of the electrode and the temperature sensor, and the anti-interference layer, enzyme layer, regulating layer, and biocompatible layer of the electrode are located in the pit. The pit can accommodate more anti-interference layers, enzyme layers, regulating layers, and biocompatible layers, thereby improving the sensitivity of the electrode. In a preferred embodiment of the present invention, the thickness of the protective layer 416 is 1 to 20 um. In a further preferred embodiment of the present invention, the thickness of the protective layer 416 is 4 um. An overly thick protective layer 416 will reduce the softness of the substrate, increase the user's discomfort after piercing the user's subcutaneous tissue, and an overly thin protective layer 416 is easily damaged.

[0129] In some embodiments of the present invention, the protective layer 416 may have a multi-layer structure. The overall thickness of the multi-layer protective layer 416 still refers to the thickness described above. When the multi-layer protective layer 416 is provided, the thickness of each protective layer 416 will become thinner.

[0130] In some embodiments of the present invention, the material of the protection layer 416 is one or more combinations of polytetrafluoroethylene, polyethylene, polyvinyl chloride, acrylonitrile-butadiene-styrene copolymer, polymethyl methacrylate, polycarbonate, and polyimide.

[0131] In some embodiments of the present invention, the material of the protective layer 416 is polyimide, which is heated appropriately to form a liquid, and then coated on a substrate made of the same polyimide material, and cured to form the protective layer 416. The protective layer 416 and the substrate made of the same material have consistent physical properties, which can prevent the protective layer 416 from being damaged or falling off due to uneven stress or stress concentration on the substrate 411.

[0132] In other embodiments of the present invention, the insulating material 414 may be disposed after the protective layer 416 is disposed. Therefore, the protective layer can prevent the metal film from warping and bubbling while increasing the strength of the substrate 411. The protective layer 416 may be disposed in a manner similar to that of the embodiment of the present invention. Figure 4a-4e That is, no matter how many layers of substrate the sensor includes, whether at least one electrode and temperature sensor are arranged on the same surface or different surfaces of the substrate, whether they are arranged in parallel or in sequence on the substrate, as long as an electrode or temperature sensor is arranged on a certain surface of a certain layer of substrate or a sub-substrate, a protective layer 416 can be arranged on that surface, but the central area of ​​the pin, electrode and / or temperature sensor needs to be exposed and at least the edges of the pin, electrode and / or temperature sensor need to be covered. Then, an insulating material 413 is arranged on the basis of the protective layer 416. The arrangement method of the insulating material can refer to Figure 3a-3fThat is, in the bent front area 414 of the uppermost A surface and / or the lowermost electrode and / or the back area 413 of the temperature sensor, if the back area of ​​the pin is not provided with a pin, and if there are areas with a large gap between the two sides of the substrate, an insulating material can also be provided later. Therefore, the method of providing a protective layer and an insulating layer on the sensor at the same time is as follows: Figure 3a-3f and Figure 4a-4e Here, only Figure 4f This is shown as an example, and other combinations are all within the protection scope of the embodiments of the present invention.

[0133] exist Figure 4f In the embodiment, the sensor includes 4 layers of substrates, and the three electrodes and the temperature sensor are arranged on the 4 layers of substrates, wherein the reference electrode, the counter electrode and the working electrode are arranged on the A surface of the sub-substrates 411d, 411c, and 411b, respectively, and the temperature sensor is arranged on the B surface of the sub-substrate 411a. The working electrode and the temperature sensor are at the same depth of puncturing the subcutaneous tissue, and the lead wire can be arranged on the surface or inner layer of the corresponding sub-substrate. A protective layer 416 is arranged on the A surface of the sub-substrates 411ab, 411c, and 411d, but the central area of ​​the pins and the electrodes is exposed. A protective layer 416 is also arranged on the B surface of the sub-substrate 411a, but the central area of ​​the pins and the temperature sensor is exposed. An insulating material 414 is arranged behind the bent front area of ​​the A surface of the top substrate 411a, and an insulating material 413 is arranged behind the B surface of the bottom substrate 411d, the reverse area corresponding to the reference electrode and the counter electrode.

[0134] In various embodiments of the present invention, the counter electrode or the working electrode may be selectively embedded according to the arrangement of the electrodes and the temperature sensor on each substrate.

[0135] In summary, the present invention discloses a high-reliability analyte sensor with integrated temperature detection. The temperature sensor is arranged on the surface of the inner part of the substrate, and can directly measure the temperature of the analyte sensor during in vivo detection. There is no need to further calibrate the detected temperature, omitting the temperature processing process, thereby improving the reliability of the detected temperature. According to the detected in vivo temperature, the analyte value can be directly calibrated to improve the accuracy of analyte detection. At the same time, at least one protective layer is arranged on the surface of the substrate, and the protective layer at least covers the edges of the electrode and / or the temperature sensor, thereby increasing the adhesion between the edges of the electrode and / or the temperature sensor and the substrate, and preventing the edges of the electrode from warping, bubbling, and falling off. At the same time, the protective layer can also increase the mechanical strength of the sensor substrate, thereby extending the service life of the sensor and improving the detection reliability of the sensor.

[0136] Although some specific embodiments of the present invention have been described in detail by way of example, it will be appreciated by those skilled in the art that the above examples are for illustration only and are not intended to limit the scope of the present invention. It will be appreciated by those skilled in the art that the above embodiments may be modified without departing from the scope and spirit of the present invention. The scope of the present invention is defined by the appended claims.

Claims

1. An analyte sensor, characterized in that: include: at least one substrate, including an internal portion and an external portion; At least two electrodes are disposed on the surface of the internal body part and are used to penetrate subcutaneously to obtain analyte parameter information; Pins, the pins are arranged on the surface of the external part and are electrically connected to the corresponding electrodes through wires; and The temperature sensor is arranged on the surface of the internal body part of the substrate, and the user detects the internal temperature of the patient; wherein at least one protective layer is arranged on the surface of the substrate, and the protective layer at least covers the edges of the two electrodes and / or the temperature sensor.

2. The analyte sensor according to claim 1, characterized in that The protection layer also covers the edges of the pins.

3. The analyte sensor according to claim 2, characterized in that The thickness of the protective layer is 1-20 um.

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

5. The analyte sensor according to claim 1, characterized in that Before the protective layer is provided, a liquid polyimide protective layer is also provided on the temperature sensor.

6. The analyte sensor according to claim 1, characterized in that The temperature sensor is one of a metal film thermal resistor, a carbon film resistor, a metal oxide film thermal resistor, and an alloy film thermal resistor.

7. The analyte sensor according to claim 6, characterized in that The temperature sensor is a thin film platinum thermal resistor.

8. The analyte sensor according to any one of claims 1 to 7, characterized in that: The at least two electrodes include at least a working electrode and a counter electrode.

9. The analyte sensor according to claim 8, characterized in that The working electrode and the temperature sensor are at the same depth of penetration into the subcutaneous tissue.

10. The analyte sensor according to claim 9, characterized in that The at least one substrate is a single-layer substrate, and the working electrode and the temperature sensor are arranged in parallel on the same surface of the single-layer substrate.

11. The analyte sensor according to claim 9, characterized in that The at least one substrate is a single-layer substrate, and the working electrode and the temperature sensor are arranged on different surfaces of the single-layer substrate.

12. The analyte sensor according to claim 9, characterized in that The at least one substrate layer comprises a multi-layer substrate, and the working electrode and the temperature sensor are arranged in parallel on the same surface of the secondary substrate in the same layer.

13. The analyte sensor according to claim 9, characterized in that The at least one substrate layer comprises a multi-layer substrate, and the working electrode and the temperature sensor are arranged on different surfaces of the same layer of the secondary substrate.

14. The analyte sensor according to claim 9, characterized in that The at least one substrate layer comprises a multi-layer substrate, and the working electrode and the temperature sensor are arranged on different surfaces of the secondary substrate in different layers.

15. The analyte sensor according to claim 14, characterized in that The working electrode and the temperature sensor are arranged on different surfaces of the secondary substrate in different adjacent layers.

16. The analyte sensor according to claim 14, characterized in that The working electrode and the temperature sensor are arranged on different surfaces of the sub-substrate at different layers.

17. The analyte sensor according to any one of claims 12 to 16, characterized in that: The multi-layered substrate is prefabricated and pasted into a whole.

18. The analyte sensor according to claim 9, characterized in that The temperature sensor is embedded in the working electrode or the counter electrode.

19. The analyte sensor according to claim 1, wherein: The conductive wire is disposed on the surface of the substrate.

20. The analyte sensor according to claim 1, wherein The conductive wire is disposed in an inner layer of the substrate.

21. The analyte sensor according to claim 1, characterized in that: At least one layer of insulating material is disposed behind at least one area of ​​the substrate surface, the insulating material avoiding the pins, the electrodes and the central conductive area of ​​the temperature sensor.

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