Analyte sensor based on monitoring blood glucose

Abstract

The invention provides an analyte sensor based on blood glucose monitoring. The analyte sensor comprises a substrate, a working electrode, a reference electrode, a counter electrode and a sensing layer, the sensing layer is arranged on the working electrode; the working electrode, the reference electrode and the counter electrode are arranged on the two sides of the substrate respectively, and the two electrodes located on the same side of the substrate are separated by a channel in space. The analyte sensor can be implanted into a human body for monitoring, and has the characteristics of good flexibility, small size, low manufacturing cost, simple process flow and long-term monitoring.

Description

Technical Field

[0001] The present invention belongs to the technical field of sensors, and in particular relates to an analyte sensor based on monitoring blood sugar. Background Art

[0002] Flexible electrodes refer to electrodes made of flexible substrates. Biosensors made of flexible electrodes have the characteristics of light weight, high softness, stretchability and excellent comfort. Biosensors made of flexible electrodes are widely used in the detection of in vitro nucleic acids, proteins, glucose, bacteria, toxins, cells and pesticides.

[0003] At present, most flexible electrodes are used for temporary in vitro detection. With the increasing demand, people are increasingly in need of sensors that can continuously monitor analytes in the body. However, the current flexible electrodes are large in size and cannot meet the human body's adaptability to sensors. At the same time, the complex manufacturing process and high manufacturing cost of sensors further limit the development of analyte sensors. Summary of the invention

[0004] In order to improve the deficiencies of the prior art, the present invention provides an analyte sensor based on monitoring blood glucose. The analyte sensor can be implanted in the human body to monitor the analyte, and the analyte sensor has the characteristics of good flexibility, small size, low manufacturing cost, simple process flow, and long-term monitoring.

[0005] The object of the present invention is achieved through the following technical solutions:

[0006] An analyte sensor, comprising a substrate, a working electrode, a reference electrode, a counter electrode and a sensing layer; the sensing layer is arranged on the working electrode; the working electrode, the reference electrode and the counter electrode are respectively arranged on both sides of the substrate, and the two electrodes located on the same side of the substrate are spatially separated by a channel;

[0007] The width of the channel is 1 μm-280 μm; the length of the channel is 30 μm-10000 μm.

[0008] According to the present invention, the analyte sensor is, for example, a sensor for analyzing blood sugar, such as a blood sugar sensor.

[0009] Beneficial effects of the present invention:

[0010] The present invention provides an analyte sensor based on monitoring blood glucose. The analyte sensor contains a channel structure, and the analyte sensor can be implanted in the human body for monitoring. The analyte sensor has the characteristics of good flexibility, small size, low manufacturing cost, simple process flow, and long-term monitoring. The introduction of the channel structure of the present invention makes the thickness of the analyte sensor more suitable and the wearing experience is better. At the same time, the introduction of the channel structure can avoid the problem of unstable signal transmission caused by the small area of ​​the electrode or the narrow electrode wire, resulting in poor stability of the sensor. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 2 is a view of the sensor electrode structure A of Example 1.

[0012] Figure 2 Schematic diagram of the structure of the AA' section of the sensor electrode structure A of Example 1.

[0013] Figure 3 Schematic diagram of the structure of the BB' section of the sensor electrode structure A of Example 1.

[0014] Figure 4 Schematic diagram of the structure of the CC' section of the sensor electrode structure A of Example 1.

[0015] Figure 5 This is a graph showing the changing trend of blood sugar after the sensor electrode structure A of Example 1 is implanted in a human body for 14 days.

[0016] Figure 6 This is a view of sensor electrode structure B of Example 2.

[0017] Figure 7 Schematic diagram of the structure of the AA' section of the sensor electrode structure B of Example 2.

[0018] Figure 8 Schematic diagram of the structure of the BB' section of the sensor electrode structure B of Example 2.

[0019] Fig. 9 Schematic diagram of the structure of the CC' section of the sensor electrode structure B of Example 2.

[0020] Fig.10 3 is a view of a sensor electrode structure C of Example 3.

[0021] Fig.11 Schematic diagram of the structure of the AA' section of the sensor electrode structure C of Example 3.

[0022] Fig.12 Schematic diagram of the structure of the BB' section of the sensor electrode structure C of Example 3.

[0023] Fig.13 Schematic diagram of the structure of the CC' section of the sensor electrode structure C of Example 3.

[0024] Fig.14 This is a view of a sensor electrode structure D of Example 4.

[0025] Fig.15 Schematic diagram of the structure of the AA' section of the sensor electrode structure D of Example 4.

[0026] Fig.16 Schematic diagram of the structure of the BB' section of the sensor electrode structure D of Example 4.

[0027] Fig.17 Schematic diagram of the structure of the CC' section of the sensor electrode structure D of Example 4.

[0028] Fig.18 This is a view of the sensor electrode structure E of Example 5.

[0029] Fig.19 Schematic diagram of the structure of the AA' section of the sensor electrode structure E of Example 5.

[0030] Fig. 20 Schematic diagram of the structure of the BB' section of the sensor electrode structure E of Example 5.

[0031] Fig.21 Schematic diagram of the structure of the CC' section of the sensor electrode structure E of Example 5.

[0032] Fig. 22 This is a view of the sensor electrode structure F of Example 6.

[0033] Fig.23 Schematic diagram of the structure of the AA' section of the sensor electrode structure F of Example 6.

[0034] Fig.24 Schematic diagram of the structure of the BB' section of the sensor electrode structure F of Example 6.

[0035] Fig.25 Schematic diagram of the structure of the CC' section of the sensor electrode structure F of Example 6.

[0036] Fig.26 This is a view of the sensor electrode structure G of Example 7.

[0037] Fig. 27 Schematic diagram of the structure of the AA' section of the sensor electrode structure G of Example 7.

[0038] Fig.28Schematic diagram of the structure of the BB' section of the sensor electrode structure G of Example 7.

[0039] Fig.29 Schematic diagram of the structure of the CC' section of the sensor electrode structure G of Example 7.

[0040] Fig.30 3 is a view of a sensor electrode structure H of Example 8.

[0041] Fig.31 Schematic diagram of the structure of the AA' section of the sensor electrode structure H of Example 8.

[0042] Fig.32 Schematic diagram of the structure of the BB' section of the sensor electrode structure H of Example 8.

[0043] Fig.33 Schematic diagram of the structure of the CC' section of the sensor electrode structure H of Example 8.

[0044] Fig.34 A partial view of the protrusion position of the sensor of the present invention.

[0045] Fig.35 The diagrams are a schematic diagram of a sensor with a protruding structure and an auxiliary device in combination (left figure) and a schematic diagram of a sensor without a protruding structure and an auxiliary device in combination (right figure), wherein reference numeral 1000 is an auxiliary device and 1001 is a sensor.

[0046] Fig.36 Schematic diagram of the structure of the sensor surface after the sensor with a protrusion structure is implanted into the human body (left figure) and the schematic diagram of the structure of the sensor surface after the sensor without a protrusion structure is implanted into the human body (right figure).

[0047] Fig.37 Schematic diagram of the structure of the sensor after implanting a sensor with a channel structure into a human body (left figure) and schematic diagram of the structure of the sensor after implanting a sensor without a channel structure (i.e., a stacked structure) into a human body (right figure).

[0048] Fig.38 This is a partially enlarged view of the sensor described in the preferred embodiment of the present invention.

[0049] Fig.39 This is a graph showing the changing trend of blood sugar monitored by the working electrode of the sensor electrode structure of Comparative Example 1 implanted in the human body for one day.

[0050] Fig.40 This is a graph showing the changing trend of blood sugar monitored by the working electrode of the sensor electrode structure of Comparative Example 2 implanted in the human body for 2 days. DETAILED DESCRIPTION

[0051] <Analyte Sensor>

[0052] As mentioned above, the present invention provides an analyte sensor, which includes a substrate 100, a working electrode, a reference electrode, a counter electrode and a sensing layer 115; the sensing layer 115 is arranged on the working electrode; the working electrode, the reference electrode and the counter electrode are respectively arranged on both sides of the substrate 100, and the two electrodes located on the same side of the substrate 100 are spatially separated by a channel 114.

[0053] According to an embodiment of the present invention, the working electrode, the reference electrode and the counter electrode are respectively arranged on both sides of the substrate 100, that is, any two electrodes among the working electrode, the reference electrode and the counter electrode are located on the same side of the substrate 100; such a structural arrangement enables two functional regions / electrode regions with different functions to exist on the first surface of the sensor, and the two functional regions / electrode regions with different functions are separated in space by the channel 114, and will not affect each other, so that the functions of the two functional regions / electrode regions can be realized on the same side surface of the sensor, and there is one functional region / electrode region on the second surface of the sensor opposite to the first surface. Such a structural arrangement can ensure that the functional region / electrode region of the sensor has sufficient area, thereby making the sensor have good stability during long-term monitoring; in addition, the structural arrangement of the two functional regions / electrode regions on the same side surface of the sensor can also make the preparation process of the sensor relatively simple, and at the same time ensure that the obtained sensor has good flexibility, small size and low cost; and due to the arrangement of the reference electrode, the analyte sensor can realize long-term monitoring of the analyte after being implanted in the body.

[0054] The study found that if the working electrode, reference electrode and counter electrode are set on the same side surface of the substrate, due to the limited implantation width of the sensor itself, the area of ​​each electrode itself and the electrode wires will be too narrow, which may easily cause problems such as short circuit and open circuit. If the working electrode, reference electrode and counter electrode are designed according to a stacked structure (that is, the spatial positions of two electrodes are in an upper and lower relationship, separated by a dielectric layer in the middle, and there is no spatial channel structure), this structure increases the process flow and difficulty, and the thickness is thicker, which will affect the wearing experience and reduce the stability of the sensor. However, the present application sets two functional areas on the same side of the substrate and separates them in space with a channel, which can not only ensure that the area of ​​the electrode itself is sufficient, but also avoid the occurrence of problems such as electrode short circuit and open circuit; at the same time, due to the moderate thickness of the electrode, the wearing experience of the analyte sensor will be better and the stability will be higher.

[0055] According to an embodiment of the present invention, the working electrode, the reference electrode and the counter electrode are respectively arranged on both sides of the substrate 100, forming a structure in which two electrodes are arranged on the first surface of the substrate 100, and one electrode is arranged on the second surface of the substrate 100 opposite to the first surface. The two electrodes refer to any two of the working electrode, the reference electrode and the counter electrode; the one electrode refers to the remaining one electrode except the above two electrodes.

[0056] According to an embodiment of the present invention, the working electrode, reference electrode and counter electrode are respectively arranged on both sides of the substrate, for example, the working electrode and the reference electrode are arranged on the first surface of the substrate, the working electrode and the reference electrode are spatially separated by a channel, and the counter electrode is arranged on the second surface of the substrate opposite to the first surface; or the working electrode and the counter electrode are arranged on the first surface of the substrate, the working electrode and the counter electrode are spatially separated by a channel, and the reference electrode is arranged on the second surface of the substrate opposite to the first surface; or the counter electrode and the reference electrode are arranged on the first surface of the substrate, the counter electrode and the reference electrode are spatially separated by a channel, and the working electrode is arranged on the second surface of the substrate opposite to the first surface.

[0057] According to an embodiment of the present invention, the two electrodes located on the same side of the substrate are located on the same plane. Specifically, the electrode layers, electrode wires and electrode contacts of the two electrodes are all located on the same plane.

[0058] According to an embodiment of the present invention, the two electrode parts located on the same side of the substrate are located on the same plane. Exemplarily, the electrode layers of the two electrodes are not located on the same plane, but the electrode wires and electrode contacts of the two electrodes are located on the same plane; or the electrode wires of the two electrodes are not located on the same plane, but the electrode layers and electrode contacts of the two electrodes are located on the same plane; or the electrode contacts of the two electrodes are not located on the same plane, but the electrode wires and electrode layers of the two electrodes are located on the same plane; or the electrode layers and electrode contacts of the two electrodes are not located on the same plane, but the electrode wires of the two electrodes are located on the same plane; or the electrode wires and electrode contacts of the two electrodes are not located on the same plane, but the electrode layers of the two electrodes are located on the same plane; or the electrode wires and electrode layers of the two electrodes are not located on the same plane, but the electrode contacts of the two electrodes are located on the same plane.

[0059] According to an embodiment of the present invention, the working electrode, the reference electrode and the counter electrode are not arranged in a stacked manner, that is, the working electrode, the reference electrode and the counter electrode are not stacked on each other. Even if the two electrodes on the same side of the substrate are partially located on the same plane, they are not stacked on each other, but are separated in space; more specifically, the two electrodes on the same side of the substrate are located in the same plane and are separated in space by a channel; or the two electrodes on the same side of the substrate are partially located in the same plane and are separated in space by a channel.

[0060] <Structure and composition of substrate>

[0061] According to an embodiment of the present invention, the substrate 100 includes a front end 101, a middle end 102 and a terminal end 103, and the front end 101, the middle end 102 and the terminal end 103 are sequentially connected and arranged.

[0062] According to an embodiment of the present invention, the substrate 100 has an L-shape, the L-shape includes a first side and a second side, and the connection between the first side and the second side forms an angle, and the angle is 45°-135°, preferably 88°-98°, such as 90°, 92°, 93°, 94°, 95°, 96°, 97° or 98°.

[0063] According to an embodiment of the present invention, the front end 101 is located on the first side and at the non-connected end of the first side, the end 103 is located on the second side and at the non-connected end of the second side, and the middle end 102 is located on the first side and the second side and at the connected end of the first side and the connected end of the second side. The connected end refers to the end close to the connection between the first side and the second side, and the non-connected end refers to the end away from the connection between the first side and the second side.

[0064] According to an embodiment of the present invention, the material forming the substrate includes at least one of plastic (such as polyethylene terephthalate PET, polyimide PI, polyvinyl chloride PVC or polyethylene PE), polydimethylsiloxane PDMS, ceramics, glass, paper and textiles.

[0065] According to an embodiment of the present invention, the length of the second side of the L-shaped substrate is 1mm-40mm, the length of the first side of the L-shaped substrate is 0.05mm-20mm, and the thickness of the substrate is 20μm-5000μm; preferably, the length of the second side of the L-shaped substrate is 2mm-30mm, the length of the first side of the L-shaped substrate is 0.10mm-10mm, and the thickness of the substrate is 50μm-2000μm; exemplarily, the length of the second side of the L-shaped substrate is 3mm, 4mm, 5mm, 8mm, 10mm, 12mm, 15mm, 18mm, 20mm, 25mm, 28mm or 30mm; the length of the first side of the L-shaped substrate is 0.10mm, 0.5mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 8mm or 10mm.

[0066] <Structure and composition of working electrode>

[0067] According to an embodiment of the present invention, the working electrode includes a working electrode layer 107 , a working electrode wire 108 and a working electrode contact 109 , and the working electrode layer 107 is connected to the working electrode contact 109 via the working electrode wire 108 .

[0068] Exemplarily, the working electrode layer 107 is located at the front end 101 of the substrate, the working electrode wire 108 is located at the middle end 102 of the substrate, and the working electrode contact 109 is located at the end 103 of the substrate; alternatively, the working electrode layer 107 and the working electrode wire 108 are located at the middle end 102 of the substrate, and the working electrode contact 109 is located at the end 103 of the substrate.

[0069] According to an embodiment of the present invention, a sensing layer 115 is disposed on the working electrode layer, and the working electrode mainly plays a role of reacting with blood sugar.

[0070] According to an embodiment of the present invention, the material forming the working electrode includes one or more of carbon, gold, silver, copper and their composite materials; or, the material forming the working electrode includes one or more of noble metals, transition metals, transition metal oxides and transition metal hydroxides having catalytic / signal conversion effects. Exemplarily, the noble metals include gold and its composite materials, platinum and its composite materials; the transition metals include copper and its composite materials, nickel and its composite materials, cobalt and its composite materials, zinc and its composite materials, manganese and its composite materials, etc.

[0071] According to an embodiment of the present invention, the working electrode is modified onto the substrate by process methods including but not limited to printing, inkjet printing, electrohydrogen jet printing (EHD), dispensing, spraying, chemical vapor deposition (CVD), physical vapor deposition (PVD), magnetron sputtering, molecular beam epitaxy, electrochemical deposition, electroplating and evaporation.

[0072] According to an embodiment of the present invention, the thickness of the working electrode layer is 1 μm-20 μm, preferably 5 μm-15 μm, for example, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 11 μm, 12 μm, 15 μm or 18 μm.

[0073] <Structure and composition of reference electrode>

[0074] According to an embodiment of the present invention, the reference electrode includes a reference electrode layer 113 , a reference electrode wire 110 and a reference electrode contact 112 , wherein the reference electrode layer 113 is disposed on the reference electrode wire 110 , and the reference electrode wire 110 is connected to the reference electrode contact 112 .

[0075] Exemplarily, the reference electrode layer 113 is located at the front end 101 of the substrate, the reference electrode wire 110 is located at the front end 101 and the middle end 102 of the substrate, and the reference electrode contact 112 is located at the end 103 of the substrate; alternatively, the reference electrode layer 113 and the reference electrode wire 110 are located at the middle end 102 of the substrate, and the reference electrode contact 112 is located at the end 103 of the substrate.

[0076] According to an embodiment of the present invention, the reference electrode forms a voltage loop with the working electrode to provide a guarantee for converting the blood glucose signal into an electrochemical signal. The reference electrode plays a role in stabilizing the potential, and thus the analyte sensor has the function and role of continuous and stable monitoring.

[0077] According to an embodiment of the present invention, the material forming the reference electrode includes Ag and AgCl, wherein the mass ratio of the Ag to the AgCl is 1:10-10:1, preferably 2:8-8:2, for example, 3:7, 4:6, 5:5, 6:4, 7:3.

[0078] According to an embodiment of the present invention, the reference electrode is modified onto the substrate by process methods including but not limited to printing, inkjet printing, electrohydrogen jet printing (EHD), dispensing, spraying, chemical vapor deposition (CVD), physical vapor deposition (PVD), magnetron sputtering, molecular beam epitaxy, electrochemical deposition, electroplating and evaporation.

[0079] According to an embodiment of the present invention, the thickness of the reference electrode layer is 0.1μm-500μm, preferably 1μm-200μm, such as 5μm, 10μm, 15μm, 20μm, 50μm, 80μm, 90μm, 100μm, 120μm, 150μm, 180μm or 200μm.

[0080] <Structure and composition of counter electrode>

[0081] According to an embodiment of the present invention, the counter electrode includes a counter electrode layer 104 , a counter electrode wire 105 and a counter electrode contact 106 , and the counter electrode layer 104 is connected to the counter electrode contact 106 via the counter electrode wire 105 .

[0082] Exemplarily, the counter electrode layer 104 is located at the front end 101 of the substrate, the counter electrode wire 105 is located at the middle end 102 of the substrate, and the counter electrode contact 106 is located at the end 103 of the substrate; or, the counter electrode layer 104 and the counter electrode wire 105 are located at the middle end 102 of the substrate, and the counter electrode contact 106 is located at the end 103 of the substrate.

[0083] According to an embodiment of the present invention, the function of the counter electrode is to form a current closed loop with the working electrode, thereby providing a guarantee for converting the blood glucose signal into an electrochemical signal.

[0084] According to an embodiment of the present invention, the material forming the counter electrode includes one or more of carbon, gold, silver, copper and composite materials thereof.

[0085] According to an embodiment of the present invention, the electrode is modified onto the substrate by process methods including but not limited to printing, inkjet printing, electrohydrogen jet printing (EHD), dispensing, spraying, chemical vapor deposition (CVD), physical vapor deposition (PVD), magnetron sputtering, molecular beam epitaxy, electrochemical deposition, electroplating and evaporation.

[0086] According to an embodiment of the present invention, the thickness of the counter electrode layer is 1 μm-20 μm, preferably 5 μm-15 μm, for example, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 11 μm, 12 μm, 15 μm or 18 μm.

[0087] <Sensing Layer>

[0088] According to an embodiment of the present invention, the sensing layer 115 is disposed on the working electrode layer 107 of the working electrode.

[0089] According to an embodiment of the present invention, the material forming the sensing layer 115 includes one or more of glucose oxidase, glucose dehydrogenase, noble metals, transition metals, transition metal oxides and transition metal hydroxides. Exemplarily, the noble metals include gold and its composite materials, platinum and its composite materials; the transition metals include copper and its composite materials, nickel and its composite materials, cobalt and its composite materials, osmium and its composite materials, zinc and its composite materials, manganese and its composite materials, iron and its composite materials.

[0090] According to an embodiment of the present invention, the sensing layer is formed on the working electrode by processes including but not limited to adsorption, printing, inkjet printing, electrohydrodynamic printing (EHD), dispensing, spraying, chemical vapor deposition (CVD), physical vapor deposition (PVD), magnetron sputtering, molecular beam epitaxy, electrochemical deposition, evaporation and the like.

[0091] According to an embodiment of the present invention, the thickness of the sensing layer is 1 μm-20 μm, preferably 1 μm-10 μm, for example, 1 μm, 2 μm, 3 μm, 4 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 11 μm, 12 μm, 15 μm or 18 μm.

[0092] According to an embodiment of the present invention, the analyte that the sensing layer can monitor is blood glucose.

[0093] <Electrode Setup>

[0094] In the context of the present invention, the working electrode, the counter electrode and the reference electrode being spatially separated by a channel preferably means that the electrode layer of one electrode and the electrode lead of the other electrode of the two electrodes located on the same side of the substrate are spatially separated by a channel.

[0095] According to an embodiment of the present invention, the electrodes located on the same side of the substrate are, for example, a working electrode and a reference electrode, and the working electrode layer 107 of the working electrode is located at the front end 101 of the substrate, the reference electrode layer 113 of the reference electrode is located at the middle end 102 of the substrate, and the reference electrode and the working electrode are spatially separated by a channel; or the working electrode layer 107 of the working electrode is located at the middle end 102 of the substrate, the reference electrode layer 113 of the reference electrode is located at the front end 101 of the substrate, and the reference electrode and the working electrode are spatially separated by a channel.

[0096] According to an embodiment of the present invention, the electrodes located on the same side of the substrate are, for example, a working electrode and a counter electrode, and the working electrode layer 107 of the working electrode is located at the front end 101 of the substrate, the counter electrode layer 104 of the counter electrode is located at the middle end 102 of the substrate, and the counter electrode and the working electrode are spatially separated by a channel; or the working electrode layer 107 of the working electrode is located at the middle end 102 of the substrate, the counter electrode layer 104 of the counter electrode is located at the front end 101 of the substrate, and the counter electrode and the working electrode are spatially separated by a channel.

[0097] According to an embodiment of the present invention, the electrodes located on the same side of the substrate are, for example, a counter electrode and a reference electrode, and the reference electrode layer 113 of the reference electrode is located at the front end 101 of the substrate, the counter electrode layer 104 of the counter electrode is located at the middle end 102 of the substrate, and the reference electrode and the counter electrode are spatially separated by a channel; or the reference electrode layer 113 of the reference electrode is located at the middle end 102 of the substrate, the counter electrode layer 104 of the counter electrode is located at the front end 101 of the substrate, and the reference electrode and the counter electrode are spatially separated by a channel.

[0098] According to an embodiment of the present invention, when the electrodes located on the same side of the substrate are a working electrode and a reference electrode, the working electrode and the reference electrode are spatially separated by a channel; illustratively, when the working electrode layer 107 of the working electrode is located at the front end 101 of the substrate and the reference electrode layer 113 of the reference electrode is located at the middle end 102 of the substrate, the reference electrode layer 113 of the reference electrode and the working electrode wire 108 of the working electrode are separated by a channel; when the working electrode layer 107 of the working electrode is located at the middle end 102 of the substrate and the reference electrode layer 113 of the reference electrode is located at the front end 101 of the substrate, the reference electrode wire 110 of the reference electrode and the working electrode layer 107 of the working electrode are spatially separated by a channel.

[0099] According to an embodiment of the present invention, when the electrodes located on the same side of the substrate are a working electrode and a counter electrode, the working electrode and the counter electrode are spatially separated by a channel; illustratively, when the working electrode layer 107 of the working electrode is located at the front end 101 of the substrate and the counter electrode layer 104 of the counter electrode is located at the middle end 102 of the substrate, the counter electrode layer 104 of the counter electrode and the working electrode wire 108 of the working electrode are separated by a channel; when the working electrode layer 107 of the working electrode is located at the middle end 102 of the substrate and the counter electrode layer 104 of the counter electrode is located at the front end 101 of the substrate, the counter electrode wire 105 of the counter electrode and the working electrode layer 107 of the working electrode are spatially separated by a channel.

[0100] According to an embodiment of the present invention, when the electrodes located on the same side of the substrate are a counter electrode and a reference electrode, the counter electrode and the reference electrode are spatially separated by a channel; illustratively, when the reference electrode layer 113 of the reference electrode is located at the front end 101 of the substrate and the counter electrode layer 104 of the counter electrode is located at the middle end 102 of the substrate, the counter electrode layer 104 of the counter electrode and the reference electrode wire 110 of the reference electrode are separated by a channel; when the reference electrode layer 113 of the reference electrode is located at the middle end 102 of the substrate and the counter electrode layer 104 of the counter electrode is located at the front end 101 of the substrate, the counter electrode wire 105 of the counter electrode and the reference electrode layer 113 of the reference electrode are spatially separated by a channel.

[0101] According to an embodiment of the present invention, when the electrodes located on the same side of the substrate are the working electrode and the reference electrode, the working electrode and the reference electrode are located on the same plane, specifically, the working electrode layer 107 of the working electrode, the working electrode wire 108 of the working electrode, the working electrode contact 109 of the working electrode, the reference electrode layer 113 of the reference electrode, the reference electrode wire 110 of the reference electrode and the reference electrode contact 112 of the reference electrode are all located on the same plane; or, the working electrode and the reference electrode are partially located on the same plane, specifically, at least one component of the electrode layers of the working electrode and the reference electrode, the electrode wires of the working electrode and the reference electrode, and the electrode contacts of the working electrode and the reference electrode are not located on the same plane; for example, the electrode layer of the working electrode and the electrode layer of the reference electrode are not located on the same plane, the electrode wire of the working electrode and the electrode wire of the reference electrode are located on the same plane, and the electrode contact of the working electrode and the electrode contact of the reference electrode are located on the same plane.

[0102] According to an embodiment of the present invention, when the electrodes located on the same side of the substrate are the working electrode and the counter electrode, the working electrode and the counter electrode are located on the same plane, specifically, the working electrode layer 107 of the working electrode, the working electrode wire 108 of the working electrode, the working electrode contact 109 of the working electrode, the counter electrode layer 104 of the counter electrode, the counter electrode wire 105 of the counter electrode and the counter electrode contact 106 of the counter electrode are all located on the same plane; or, the working electrode and the counter electrode are partially located on the same plane, specifically, at least one component of the electrode layers of the working electrode and the counter electrode, the electrode wires of the working electrode and the counter electrode and the electrode contacts of the working electrode and the counter electrode are not located on the same plane; for example, the electrode layer of the working electrode and the electrode layer of the counter electrode are not located on the same plane, the electrode wire of the working electrode and the electrode wire of the counter electrode are located on the same plane, and the electrode contact of the working electrode and the electrode contact of the counter electrode are located on the same plane.

[0103] According to an embodiment of the present invention, when the electrodes located on the same side of the substrate are the counter electrode and the reference electrode, the counter electrode and the reference electrode are located on the same plane, specifically, the counter electrode layer 104 of the counter electrode, the counter electrode wire 105 of the counter electrode, the counter electrode contact 106 of the counter electrode, the reference electrode layer 113 of the reference electrode, the reference electrode wire 110 of the reference electrode and the reference electrode contact 112 of the reference electrode are all located on the same plane; or, the counter electrode and the reference electrode are partially located on the same plane, specifically, at least one component of the electrode layers of the counter electrode and the reference electrode, the electrode wires of the counter electrode and the reference electrode, and the electrode contacts of the counter electrode and the reference electrode are not located on the same plane; for example, the electrode layer of the counter electrode and the electrode layer of the reference electrode are not located on the same plane, the electrode wire of the counter electrode and the electrode wire of the reference electrode are located on the same plane, and the electrode contact of the counter electrode and the electrode contact of the reference electrode are located on the same plane.

[0104] <Channel Structure>

[0105] According to an embodiment of the present invention, Fig.38 As shown, the width of the channel 114 refers to the distance between the electrode layer of one electrode and the electrode wire of the other electrode in the two electrodes separated by the channel in space, as shown in FIG. Fig.38The middle line segment "W" represents the width of the channel 114; the specific electrode layers and electrode wires need to be determined according to the different arrangements of the working electrode, reference electrode and counter electrode inside the sensor; illustratively, the width of the channel 114 refers to the distance between the counter electrode wire 105 of the counter electrode and the reference electrode layer 113 of the reference electrode; or the distance between the counter electrode wire 105 of the counter electrode and the working electrode layer 107 of the working electrode; or the distance between the working electrode wire 108 of the working electrode and the counter electrode layer 104 of the counter electrode; or the distance between the working electrode wire 108 of the working electrode and the reference electrode layer 113 of the reference electrode; or the distance between the reference electrode wire 110 of the reference electrode and the working electrode layer 107 of the working electrode; or the distance between the reference electrode wire 110 of the reference electrode and the counter electrode layer 104 of the counter electrode.

[0106] According to an embodiment of the present invention, the width of the channel 114 can be fixed or gradual. If it is fixed, the width of the channel is a fixed value in the range of 1μm-280μm. If it is gradual, the width of the channel 114 gradually increases or decreases along the direction from the front end 101 of the substrate to the middle end 102 of the substrate, and the width of the channel changes within a width variation range of 1μm-280μm, for example, changes within a width range of 50μm-150μm or changes within a width range of 80μm-200μm.

[0107] According to an embodiment of the present invention, the width of the channel is 1μm-280μm, preferably 50μm-170μm, for example, 20μm, 30μm, 40μm, 50μm, 60μm, 70μm, 80μm, 90μm, 100μm, 110μm, 120μm, 130μm, 140μm, 150μm, 160μm, 170μm, 180μm, 190μm, 200μm, 210μm, 220μm, 230μm, 240μm, 250μm, 260μm, 270μm, 280μm or a range consisting of the above two endpoints. The study found that when the width of the channel is 1μm-280μm, it can effectively separate the two electrodes located on the same side surface of the sensor, so that the functions of two functional areas / electrode areas are realized on the same side surface of the sensor, and it is beneficial to improve the stability of the sensor; when the width of the channel is less than 10μm, due to the narrowness of the channel width, there is a risk of contact between the two electrodes, resulting in a short circuit between the electrodes and thus causing the test data to be too high or too low, causing the sensor to fail; when the width of the channel is greater than 280μm, due to the wideness of the channel width, the electrode / electrode wire will be too narrow, which may lead to insufficient area of ​​the functional area / electrode area, or the electrode / electrode wire will be too narrow, resulting in an electrode break, resulting in data "jumps" or "jitters" during the sensor test, affecting the stability of the test data and causing the sensor to fail.

[0108] According to an embodiment of the present invention, Fig.38 As shown, the length of the channel 114 refers to the distance from the front end of the electrode layer located at the middle end of the substrate to the connection between the first side and the second side of the substrate, that is, Fig.38 The middle line segment "D" represents the length of the channel 114; the specific electrode layer needs to be determined according to the different arrangements of the working electrode, reference electrode and counter electrode inside the sensor; illustratively, the length of the channel 114 is the distance from the front end of the working electrode layer of the working electrode located at the middle end of the substrate to the connection between the first and second sides of the substrate; or the distance from the front end of the reference electrode layer of the reference electrode located at the middle end of the substrate to the connection between the first and second sides of the substrate; or the distance from the front end of the counter electrode layer of the counter electrode located at the middle end of the substrate to the connection between the first and second sides of the substrate.

[0109] According to an embodiment of the present invention, the length of the channel is 30 μm-10000 μm, for example, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 110 μm, 120 μm, 130 μm, 140 μm, 150 μm, 160 μm, 170 μm, 180 μm, 190 μm, 200 μm, 210 μm, 220 μm, 230 μm, 240 μm, 250 μm, 260 μm, 270 μm, 280 μm, 300 μm, 320 μm, 350 μm, 380 μm, 400 μm, 410 μm, 420 μm, 430 μm, 440 μm, 450 μm, 460 μm, 470 μm, 480 μm, 490 μm, 500 μm, 510 μm, 520 μm, 530 μm, 540 μm, 550 μm, 560 μm, 570 μm, 580 μm, 590 μm, 600 μm, 610 μm, 620 μm, 630 μm, 640 μm, 650 μm, 660 μm, 670 μm, 680 μm, 690 μm, 700 μm, 710 μm, 720 μm, 730 μm, 740 μm, 750 μm, 760 μm, 770 μm, 780 μm, 79 00μm,450μm,500μm,550μm,600μm,700μm,800μm,900μm,1000μm,1100μm,1200μm,1300μm,1400μm,1500μm,2000μm,2500μm,3 000μm, 3500μm, 4000μm, 4500μm, 5000μm, 5500μm, 6000μm, 6500μm, 7000μm, 7500μm, 8000μm, 8500μm, 9000μm, 9500μm or 10000μm. The study found that when the length of the channel is 30μm-10000μm, it can effectively monitor the monitored object and provide better wearing comfort; when the length of the channel is less than 30μm, the analyte sensor may not be able to effectively contact body fluids, and thus there is a risk of being unable to monitor; when the length of the channel is greater than 10000μm, due to excessive implantation, the wearer is prone to bleeding and pain, affecting the wearing experience.

[0110] According to an embodiment of the present invention, the channel can be obtained by printing, engraving, etching, inkjet printing, electrohydrodynamic printing (EHD), dispensing, spraying, chemical vapor deposition (CVD), physical vapor deposition (PVD), magnetron sputtering, molecular beam epitaxy, electrochemical deposition, evaporation and the like.

[0111] <Sensor Structure>

[0112] According to an embodiment of the present invention, the analyte sensor is a three-electrode system, and the combined use of the three electrodes can play a role in stabilizing the potential.

[0113] According to an embodiment of the present invention, the analyte sensor can continuously monitor for 7-360 days.

[0114] According to an embodiment of the present invention, the analyte sensor has an L shape. The L-shaped sensor can be adapted to the auxiliary device to better complete the analysis work; on the other hand, the L shape can effectively prevent the sensor from being damaged during implantation, increasing the probability of successful sensor implantation.

[0115] According to an embodiment of the present invention, the analyte sensor has an L shape, wherein the L shape includes a first side and a second side, and a connection between the first side and the second side forms an angle of 45°-135°, preferably 88°-98°.

[0116] According to an embodiment of the present invention, the first surface of the analyte sensor has two contact areas and two electrode areas, and the second surface of the analyte sensor opposite to the first surface has one contact area and one electrode area. Further, the electrode area is arranged on a first side of the L-shaped sensor, and the contact area is arranged on a second side of the sensor.

[0117] <Protrusion structure>

[0118] According to an embodiment of the present invention, the connection between the first side and the second side forms a protrusion structure 118. Preferably, the outer edge of the connection between the first side and the second side forms a protrusion structure, and the setting of the protrusion structure can make the sensor adapt to the auxiliary device during implantation, and can make the sensor implantation smoother.

[0119] According to an embodiment of the present invention, the shape of the protrusion structure can be semicircular, triangular, square or polygonal, such as Fig.34 shown.

[0120] According to an embodiment of the present invention, the number of the protrusion structure may be one or more. Fig.34 shown.

[0121] <Dielectric layer>

[0122] According to an embodiment of the present invention, the analyte sensor further includes a dielectric layer 117, which is disposed on a substrate, an electrode or an electrode wire and can be specifically adjusted according to the structure of the sensor. The dielectric layer can play an insulating role and is used to protect the working electrode, the counter electrode and the reference electrode from being damaged.

[0123] Exemplarily, the dielectric layer is arranged on the surface of the working electrode or the working electrode wire to protect the working electrode from being damaged; the dielectric layer is arranged on the surface of the reference electrode or the reference electrode wire to protect the reference electrode from being damaged; the dielectric layer is arranged on the surface of the counter electrode or the counter electrode wire to protect the counter electrode from being damaged.

[0124] According to an embodiment of the present invention, the material forming the dielectric layer includes at least one of plastic (such as polyethylene terephthalate PET, polyimide PI, polyvinyl chloride PVC or polyethylene PE), polydimethylsiloxane PDMS, ceramics, glass, paper and textiles.

[0125] According to an embodiment of the present invention, the dielectric layer is formed on the reference electrode, the working electrode wire or the counter electrode wire by processes including but not limited to adsorption, printing, inkjet printing, electrohydrogen jet printing (EHD), dispensing, spraying, chemical vapor deposition (CVD), physical vapor deposition (PVD), magnetron sputtering, molecular beam epitaxy, electrochemical deposition, evaporation and the like.

[0126] According to an embodiment of the present invention, the thickness of the dielectric layer is 1μm-1000μm, preferably 10μm-500μm, for example, 10μm, 20μm, 50μm, 80μm, 100μm, 120μm, 150μm, 180μm, 200μm, 220μm, 250μm, 260μm, 280μm, 300μm, 320μm, 350μm, 380μm, 400μm, 420μm, 450μm, 480μm, 500μm, 600μm, 700μm, 800μm, 900μm or 1000μm.

[0127] In all sensor configurations disclosed herein, the various electrodes may be isolated from each other by channels.

[0128] <Protective layer>

[0129] According to an embodiment of the present invention, the analyte sensor further includes a protective layer 116 , which is disposed at the outermost layer of the sensor.

[0130] According to an embodiment of the present invention, the protective layer may be a single-layer structure or a multi-layer structure.

[0131] According to an embodiment of the present invention, the protective layer may have the function of limiting flux. The protective layer may have the function of preventing biofouling. The protective layer may have the function of shielding environmental noise. The protective layer may have the function of protecting internal components / elements from corrosion and damage.

[0132] According to an embodiment of the present invention, the protective layer may be in a gel state or a solid state.

[0133] According to an embodiment of the present invention, the protective layer may be some component, such as a filter.

[0134] According to an embodiment of the present invention, the material forming the protective layer may be an ethylene homopolymer or an ethylene copolymer.

[0135] According to an embodiment of the present invention, the thickness of the protective layer is 0.5μm-2000μm. Preferably, the thickness of the protective layer is 2μm-1000μm, for example, 5μm, 10μm, 50μm, 80μm, 100μm, 150μm, 200μm, 250μm, 300μm, 350μm, 400μm, 450μm, 500μm, 600μm, 700μm, 800μm, 900μm or 1000μm.

[0136] According to an embodiment of the present invention, the protective layer is modified onto the sensor by processes including but not limited to dispensing, spin coating, spraying, dipping, scraping, nesting, wrapping, printing, inkjet printing, electrohydrodynamic printing (EHD), electrospinning, chemical vapor deposition (CVD), physical vapor deposition (PVD), magnetron sputtering, molecular beam epitaxy, electrochemical deposition, evaporation and the like.

[0137] <Sensor related instructions>

[0138] According to an embodiment of the present invention, the analyte sensor may use any one of the first, second, third or fourth generation technologies for monitoring blood glucose. Specifically, different detection technologies may be used to monitor blood glucose depending on the working electrode material and the sensing layer material.

[0139] According to an embodiment of the present invention, the analyte sensor may contain an enzyme.

[0140] According to an embodiment of the present invention, the analyte sensor includes a working electrode, a reference electrode and a counter electrode. The analyte sensor is implanted into the body in a minimally invasive manner using an auxiliary device. Specifically, the front end and part of the middle end (i.e., the position below the protrusion structure, one side of the L shape) of the analyte sensor are implanted into the body. The working electrode and the counter electrode are used to form a current loop, and the working electrode and the reference electrode are used to form a voltage loop, so that the sensing layer located on the working electrode generates an electrochemical signal after reacting with blood glucose, thereby achieving the purpose of monitoring blood glucose; further, there is a corresponding relationship between the strength of the generated electrochemical signal and the blood glucose concentration, that is, the higher the blood glucose concentration, the stronger the generated electrochemical signal.

[0141] According to an embodiment of the present invention, the implantation length of the analyte sensor is 1 mm-20 mm, and the width is 0.05 mm-10 mm; preferably, the implantation length of the analyte sensor is 3 mm-18 mm, and the width is 0.10 mm-8 mm.

[0142] <Detection Method for Determining Analyte>

[0143] A detection method for determining an analyte, the detection method comprising:

[0144] 1) exposing the analyte sensor to a fluid containing an analyte of different concentrations, applying a voltage to the sensor, and obtaining electrochemical signals of different signal intensities, wherein the signal intensity of the electrochemical signal is proportional to the concentration of the analyte in the fluid;

[0145] 2) Correlating the signal intensity of the electrochemical signal with the concentration of the analyte in the fluid, and drawing a standard curve of the signal intensity of the electrochemical signal and the concentration of the analyte;

[0146] 3) Exposing the analyte sensor to a fluid including the analyte to be monitored, applying voltage to the sensor to obtain an electrochemical signal, and obtaining the concentration of the analyte to be monitored in the fluid based on the signal intensity of the obtained electrochemical signal.

[0147] According to an embodiment of the present invention, the analyte is blood glucose.

[0148] The present invention will be described in further detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0149] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the reagents, materials, etc. used in the following examples, unless otherwise specified, can be obtained from commercial channels.

[0150] Example 1

[0151] The structure of the sensor electrode structure A of Example 1 is as follows Figure 1-Figure 4 shown.

[0152] Figure 1 1 is a view of the sensor electrode structure A of Example 1, wherein the left image is a back view of the sensor electrode structure A, and the right image is a front view of the sensor electrode structure A. Figure 1 As can be seen in the figure, the sensor electrode structure A comprises a substrate 100: the substrate 100 has an L-shaped structure, and the substrate 100 comprises a front end 101, a middle end 102 and a terminal end 103;

[0153] The sensor electrode structure A includes a working electrode, which includes a working electrode layer 107 located at the front end 101 of the substrate, a working electrode wire 108 located at the middle end 102 of the substrate, and a working electrode contact 109 located at the end 103 of the substrate; the sensor electrode structure A includes a sensing layer 115 located on the working electrode layer 107; the sensor electrode structure A includes a reference electrode, which includes a reference electrode layer 113 and a reference electrode wire 110 located at the middle end 102 of the substrate, and a reference electrode contact 112 located at the end 103 of the substrate, and the reference electrode layer 113 is arranged on the reference electrode wire 110; the sensor electrode structure A includes a counter electrode, which includes a counter electrode layer 104 located at the front end 101 of the substrate, a counter electrode wire 105 located at the middle end 102 of the substrate, and a counter electrode contact 106 located at the end 103 of the substrate; the counter electrode is located on the back side of the sensor electrode structure A, and the reference electrode and the working electrode are located on the front side of the sensor electrode structure A.

[0154] The sensor electrode structure A includes a channel 114 located between the working electrode wire 108 of the working electrode and the reference electrode layer 113, and the working electrode and the reference electrode are separated by the channel 114. The width of the channel 114 is adjustable within the range of 1 μm-280 μm, and the length of the channel is adjustable within the range of 30 μm-10000 μm.

[0155] The sensor electrode structure A has an L shape, including a first side and a second side, and the connection between the first side and the second side forms an angle of 85°-95°. A protrusion structure 118 is formed at the outer edge of the connection between the first side and the second side.

[0156] The sensor electrode structure A includes a protection layer 116 , which is disposed on the outside of the sensor.

[0157] Figure 2 Schematic diagram of the structure of the AA' section of the sensor electrode structure A of Example 1. Figure 3 Schematic diagram of the structure of the BB' section of the sensor electrode structure A of Example 1. Figure 4 FIG. 1 is a schematic structural diagram of the CC' section of the sensor electrode structure A of Example 1. Figure 2-Figure 4 As can be seen in the figure, the sensor electrode structure A further comprises a dielectric layer 117, and the dielectric layer 117 is arranged on the reference electrode, the working electrode wire and the counter electrode wire.

[0158] The sensor electrode structure A is implanted into the human body for long-term testing. Figure 5 This is a graph showing the trend of blood sugar changes after 14 days of implantation in the human body. Figure 5 It can be seen from the figure that the sensor can realize long-term monitoring of blood sugar.

[0159] Example 2

[0160] The structure of the sensor electrode structure B of Example 2 is as follows Figure 6-Figure 9 shown.

[0161] Figure 6 1 and 2 are views of the sensor electrode structure B of Example 2, wherein the left view is a back view of the sensor electrode structure B, and the right view is a front view of the sensor electrode structure B. Figure 7 Schematic diagram of the structure of the AA' section of the sensor electrode structure B of Example 2. Figure 8 Schematic diagram of the structure of the BB' section of the sensor electrode structure B of Example 2. Fig. 9 Schematic diagram of the structure of the CC' section of the sensor electrode structure B of Example 2.

[0162] The composition of the sensor electrode structure B is exactly the same as that of the sensor electrode structure A, except that the positional relationship between the reference electrode and the working electrode located on the front side of the sensor electrode structure is changed, that is, the sensor electrode structure B includes a working electrode, and the working electrode includes a working electrode layer 107 and a working electrode wire 108 located at the middle end 102 of the substrate, and a working electrode contact 109 located at the end 103 of the substrate;

[0163] The sensor electrode structure B includes a reference electrode, which includes a reference electrode layer 113 located at the front end 101 of the substrate, a reference electrode wire 110 located at the front end 101 of the substrate and the middle end 102 of the substrate, and a reference electrode contact 112 located at the end 103 of the substrate, and the reference electrode layer 113 is arranged on the reference electrode wire 110;

[0164] The sensor electrode structure B includes a channel 114 located between a working electrode layer 107 of the working electrode and a reference electrode wire 110 of the reference electrode, and the working electrode and the reference electrode are separated by the channel 114. The width of the channel 114 is adjustable within the range of 1 μm-280 μm, and the length of the channel is adjustable within the range of 30 μm-10000 μm.

[0165] Example 3

[0166] The structure of the sensor electrode structure C of Example 3 is as follows Figure 10-13 shown.

[0167] Fig.10 3 are views of the sensor electrode structure C of Example 3, wherein the left image is a back view of the sensor electrode structure C, and the right image is a front view of the sensor electrode structure C. Fig.10As can be seen in the figure, the sensor electrode structure C includes a substrate 100: the substrate 100 has an L-shaped structure, and the substrate 100 includes a front end 101, a middle end 102 and a terminal end 103;

[0168] The sensor electrode structure C comprises a working electrode, wherein the working electrode comprises a working electrode layer 107 located at the front end 101 of the substrate, a working electrode wire 108 located at the middle end 102 of the substrate, and a working electrode contact 109 located at the end 103 of the substrate;

[0169] The sensor electrode structure C includes a sensing layer 115 located on the working electrode layer 107;

[0170] The sensor electrode structure C includes a reference electrode, which includes a reference electrode layer 113 located at the front end 101 of the substrate, a reference electrode wire 110 located at the front end 101 of the substrate and the middle end 102 of the substrate, and a reference electrode contact 112 located at the end 103 of the substrate, and the reference electrode layer 113 is arranged on the reference electrode wire 110;

[0171] The sensor electrode structure C includes a counter electrode, and the counter electrode includes a counter electrode layer 104 located at the middle end 102 of the substrate, a counter electrode wire 105 located at the middle end 102 of the substrate, and a counter electrode contact 106 located at the end 103 of the substrate;

[0172] The reference electrode is located at the back of the sensor electrode structure C, and the counter electrode and the working electrode are located at the front of the sensor electrode structure C.

[0173] The sensor electrode structure C includes a channel 114 located between the working electrode wire 108 of the working electrode and the counter electrode layer 104, and the channel 114 is used to separate the working electrode and the counter electrode. The width of the channel 114 is adjustable within the range of 1μm-280μm, and the length of the channel is adjustable within the range of 30μm-10000μm.

[0174] The sensor electrode structure C has an L shape, including a first side and a second side, and the connection between the first side and the second side forms an angle of 85°-95°. A protrusion structure 118 is formed at the outer edge of the connection between the first side and the second side.

[0175] The sensor electrode structure C includes a protection layer 116 , which is disposed on the outside of the sensor.

[0176] Fig.11 Schematic diagram of the structure of the AA' section of the sensor electrode structure C of Example 3. Fig.12 Schematic diagram of the structure of the BB' section of the sensor electrode structure C of Example 3. Fig.13FIG. 1 is a schematic structural diagram of the CC' section of the sensor electrode structure C of Example 3. Figure 11-13 As can be seen in FIG. 1 , the sensor electrode structure C further includes a dielectric layer 117 , and the dielectric layer 117 is disposed on the reference electrode, the working electrode wire and the counter electrode wire.

[0177] Example 4

[0178] The structure of the sensor electrode structure D of Example 4 is as follows Figure 14-17 shown.

[0179] Fig.14 1 and 2 are views of the sensor electrode structure D of Example 4, wherein the left view is a back view of the sensor electrode structure D, and the right view is a front view of the sensor electrode structure D. Fig.15 Schematic diagram of the structure of the AA' section of the sensor electrode structure D of Example 4. Fig.16 Schematic diagram of the structure of the BB' section of the sensor electrode structure D of Example 4. Fig.17 Schematic diagram of the structure of the CC' section of the sensor electrode structure D of Example 4.

[0180] The composition of the sensor electrode structure D is exactly the same as that of the sensor electrode structure C, except that the positional relationship between the counter electrode and the working electrode located on the front side of the sensor electrode structure is changed, that is, the sensor electrode structure D includes a working electrode, and the working electrode includes a working electrode layer 107 and a working electrode wire 108 located at the middle end 102 of the substrate, and a working electrode contact 109 located at the end 103 of the substrate;

[0181] The sensor electrode structure D includes a counter electrode, which includes a counter electrode layer 104 located at the front end 101 of the substrate, a counter electrode wire 105 located at the middle end 102 of the substrate, and a counter electrode contact 106 located at the end 103 of the substrate.

[0182] The sensor electrode structure D includes a channel 114 between a working electrode layer 107 of the working electrode and a counter electrode conductor 105 of the counter electrode, and the working electrode and the counter electrode are separated by the channel 114. The width of the channel 114 is adjustable within the range of 1 μm-280 μm, and the length of the channel is adjustable within the range of 30 μm-10000 μm.

[0183] Example 5

[0184] The structure of the sensor electrode structure E of Example 5 is as follows Figure 18-Figure 21 shown.

[0185] Fig.181 is a view of the sensor electrode structure E of Example 5, wherein the left figure is a back view of the sensor electrode structure E, and the right figure is a front view of the sensor electrode structure E. Fig.18 As can be seen in the figure, the sensor electrode structure E includes a substrate 100: the substrate 100 has an L-shaped structure, and the substrate 100 includes a front end 101, a middle end 102 and a terminal end 103;

[0186] The sensor electrode structure E comprises a working electrode, wherein the working electrode comprises a working electrode layer 107 located at the front end 101 of the substrate, a working electrode wire 108 located at the middle end 102 of the substrate, and a working electrode contact 109 located at the end 103 of the substrate;

[0187] The sensor electrode structure E includes a sensing layer 115 located on the working electrode layer 107;

[0188] The sensor electrode structure E includes a reference electrode, which includes a reference electrode layer 113 located at the front end 101 of the substrate, a reference electrode wire 110 located at the front end 101 of the substrate and the middle end 102 of the substrate, and a reference electrode contact 112 located at the end 103 of the substrate, and the reference electrode layer 113 is arranged on the reference electrode wire 110;

[0189] The sensor electrode structure E comprises a counter electrode, and the counter electrode comprises a counter electrode layer 104 located at the middle end 102 of the substrate, a counter electrode wire 105 located at the middle end 102 of the substrate, and a counter electrode contact 106 located at the end 103 of the substrate;

[0190] The working electrode is located at the back of the sensor electrode structure E, and the reference electrode and the counter electrode are located at the front of the sensor electrode structure E.

[0191] The sensor electrode structure E includes a channel 114 located between a reference electrode wire 110 of the reference electrode and a counter electrode layer 104 of the counter electrode, and the reference electrode and the counter electrode are separated by the channel 114. The width of the channel 114 is adjustable within the range of 1 μm-280 μm, and the length of the channel is adjustable within the range of 30 μm-10000 μm.

[0192] The sensor electrode structure E has an L shape, including a first side and a second side, and the connection between the first side and the second side forms an angle of 85°-95°. A protrusion structure 118 is formed at the outer edge of the connection between the first side and the second side.

[0193] The sensor electrode structure E includes a protection layer 116 , which is disposed on the outside of the sensor.

[0194] Fig.19Schematic diagram of the structure of the AA' section of the sensor electrode structure E of Example 5. Fig. 20 Schematic diagram of the structure of the BB' section of the sensor electrode structure E of Example 5. Fig.21 FIG. 5 is a schematic structural diagram of the CC' section of the sensor electrode structure E of Example 5. Figure 19-21 As can be seen in FIG. 1 , the sensor electrode structure E further includes a dielectric layer 117 , and the dielectric layer 117 is disposed on the reference electrode, the working electrode wire and the counter electrode wire.

[0195] Example 6

[0196] The structure of the sensor electrode structure F of Example 6 is as follows Figure 22-Figure 25 shown.

[0197] Fig. 22 1 and 2 are views of the sensor electrode structure F of Example 6, wherein the left view is a back view of the sensor electrode structure F, and the right view is a front view of the sensor electrode structure F. Fig.23 Schematic diagram of the structure of the AA' section of the sensor electrode structure F of Example 6. Fig.24 Schematic diagram of the structure of the BB' section of the sensor electrode structure F of Example 6. Fig.25 Schematic diagram of the structure of the CC' section of the sensor electrode structure F of Example 6.

[0198] The composition of the sensor electrode structure F is completely the same as that of the sensor electrode structure E, except that the positional relationship between the counter electrode and the working electrode located on the front side of the sensor electrode structure is changed, that is, the sensor electrode structure F includes a reference electrode, and the reference electrode includes a reference electrode layer 113 located at the middle end 102 of the substrate, a reference electrode wire 110 at the middle end 102 of the substrate, and a reference electrode contact 112 located at the end 103 of the substrate, and the reference electrode layer 113 is arranged on the reference electrode wire 110;

[0199] The sensor electrode structure F comprises a counter electrode, and the counter electrode comprises a counter electrode layer 104 located at the front end 101 of the substrate, a counter electrode wire 105 located at the middle end 102 of the substrate, and a counter electrode contact 106 located at the end 103 of the substrate;

[0200] The sensor electrode structure F includes a channel 114 located between a reference electrode layer 113 of the reference electrode and a counter electrode wire 105 of the counter electrode, and the reference electrode and the counter electrode are separated by the channel 114. The width of the channel 114 is adjustable within the range of 1 μm-280 μm, and the length of the channel is adjustable within the range of 30 μm-10000 μm.

[0201] Example 7

[0202] The structure of the sensor electrode structure G of Example 7 is as follows Figure 26-Figure 29 shown.

[0203] Fig.26 1 is a view of the sensor electrode structure G of Example 7, wherein the left image is a back view of the sensor electrode structure G, the middle image is a middle layer view of the sensor electrode structure G, and the right image is a front view of the sensor electrode structure G. Fig.26 As can be seen in the figure, the sensor electrode structure G includes a substrate 100: the substrate 100 has an L-shaped structure, and the substrate 100 includes a front end 101, a middle end 102 and a terminal end 103;

[0204] The sensor electrode structure G comprises a working electrode, wherein the working electrode comprises a working electrode layer 107 located at the front end 101 of the substrate, a working electrode wire 108 located at the middle end 102 of the substrate, and a working electrode contact 109 located at the end 103 of the substrate;

[0205] The sensor electrode structure G includes a sensing layer 115 located on the working electrode layer 107;

[0206] The sensor electrode structure G includes a reference electrode, which includes a reference electrode layer 113 and a reference electrode wire 110 located at the substrate middle end 102, and a reference electrode contact 112 located at the substrate end 103, and the reference electrode layer 113 is arranged on the reference electrode wire 110;

[0207] The sensor electrode structure G includes a counter electrode, and the counter electrode includes a counter electrode layer 104 located at the front end 101 of the substrate, a counter electrode wire 105 located at the middle end 102 of the substrate, and a counter electrode contact 106 located at the end 103 of the substrate;

[0208] The counter electrode is located on the back of the sensor electrode structure G, the working electrode is located in the middle of the sensor electrode structure G, and the reference electrode is located on the front of the sensor electrode structure G, that is, the working electrode and the reference electrode located on the same side of the substrate 100 are not located on the same plane.

[0209] The sensor electrode structure G includes a channel 114 located between a working electrode wire 108 of the working electrode and a reference electrode layer 113, and the channel 114 is used to separate the working electrode and the reference electrode. The width of the channel 114 is adjustable within the range of 1 μm-280 μm, and the length of the channel is adjustable within the range of 30 μm-10000 μm.

[0210] The sensor electrode structure G has an L shape, including a first side and a second side, and the connection between the first side and the second side forms an angle of 85°-95°. A protrusion structure 118 is formed at the outer edge of the connection between the first side and the second side.

[0211] The sensor electrode structure G includes a protective layer 116 , which is disposed on the outside of the sensor.

[0212] Fig. 27 Schematic diagram of the structure of the AA' section of the sensor electrode structure G of Example 7. Fig.28 Schematic diagram of the structure of the BB' section of the sensor electrode structure G of Example 7. Fig.29 FIG. 1 is a schematic structural diagram of the CC' section of the sensor electrode structure G of Example 7. Figure 27-Figure 29 As can be seen in FIG. 1 , the sensor electrode structure E further includes a dielectric layer 117 , and the dielectric layer 117 is disposed on the reference electrode, the working electrode wire and the counter electrode wire.

[0213] Example 8

[0214] The structure of the sensor electrode structure H of Example 8 is as follows Figure 30-Figure 33 shown.

[0215] Fig.30 These are views of the sensor electrode structure H of Example 8, wherein the left view is a back view of the sensor electrode structure H, the middle view is a middle layer view of the sensor electrode structure H, and the right view is a front view of the sensor electrode structure H. Fig.31 Schematic diagram of the structure of the AA' section of the sensor electrode structure H of Example 8. Fig.32 Schematic diagram of the structure of the BB' section of the sensor electrode structure H of Example 8. Fig.33 Schematic diagram of the structure of the CC' section of the sensor electrode structure H of Example 8.

[0216] The composition of the sensor electrode structure H is exactly the same as that of the sensor electrode structure G, the difference being that the positional relationship between the reference electrode and the working electrode located on the front and middle layers of the sensor electrode structure has changed, that is, the counter electrode is located on the back of the sensor electrode structure G, the reference electrode is located in the middle layer of the sensor electrode structure G, and the working electrode is located on the front of the sensor electrode structure G. The working electrode and the reference electrode located on the same side of the substrate 100 are not located on the same plane.

[0217] Specifically, the sensor electrode structure H includes a working electrode, and the working electrode includes a working electrode layer 107 and a working electrode wire 108 located at the middle end 102 of the substrate, and a working electrode contact 109 located at the end 103 of the substrate;

[0218] The sensor electrode structure H includes a reference electrode, which includes a reference electrode layer 113 located at the front end 101 of the substrate, a reference electrode wire 110 located at the front end 101 of the substrate and the middle end 102 of the substrate, and a reference electrode contact 112 located at the end 103 of the substrate, and the reference electrode layer 113 is arranged on the reference electrode wire 110.

[0219] The sensor electrode structure H includes a channel 114 located between a working electrode layer 107 of a working electrode and a reference electrode wire 110 of a reference electrode, and the channel 114 is used to separate the working electrode from the reference electrode. The width of the channel 114 is adjustable within the range of 1 μm-280 μm, and the length of the channel is adjustable within the range of 30 μm-10000 μm.

[0220] Fig.35 The diagrams are a schematic diagram of a sensor with a protruding structure and an auxiliary device (left diagram) and a schematic diagram of a sensor without a protruding structure and an auxiliary device (right diagram), wherein reference numeral 1000 is an auxiliary device and 1001 is a sensor. Fig.35 It can be seen that the sensor portion without the protrusion structure is located outside the auxiliary device.

[0221] Fig.36 A schematic diagram of the structure of the sensor surface after the sensor with protrusion structure is implanted in the human body (left picture) and a schematic diagram of the structure of the sensor surface after the sensor without protrusion structure is implanted in the human body (right picture). Fig.36 It can be seen that the sensor without a protrusion structure has damage on its surface after being implanted into the human body, while the sensor with a protrusion structure has no damage on its surface after being implanted into the human body.

[0222] Fig.37 The schematic diagram of the structure of the sensor with a channel structure after being implanted into the human body (left picture) and the schematic diagram of the structure of the sensor without a channel structure (i.e., a stacked structure) after being implanted into the human body (right picture). Fig.37 It can be seen that after the sensor without a channel structure (i.e. a stacked structure) is implanted in the human body, "bloodstains" can be seen on the side of the sensor. The "bloodstains" indicate that there is obvious bleeding at the wearing position when the sensor is implanted, which affects the wearing experience from the user's perspective. The sensor with a channel structure has a more suitable thickness, so there are no obvious "bloodstains" on the side, which means that the sensor with a channel structure is smoother to wear and provides a better wearing experience.

[0223] Comparative Example 1

[0224] The other structures are as shown in Example 1, except that the width of the channel 114 in the sensor of Comparative Example 1 is less than 1 μm, which will cause the working electrode wire to contact the reference electrode, and the working electrode and the reference electrode are very likely to short-circuit. The trend of blood sugar changes after the sensor is implanted in a normal human body for one day is shown in FIG. Fig.39 As shown. Fig.39 It can be seen that due to the narrow channel width in the sensor, the working electrode and the reference electrode are very likely to short-circuit, which will lead to high blood sugar. The blood sugar reading of a normal person is generally between 3.9mM-6.1mM.

[0225] Comparative Example 2

[0226] The other structures are as shown in Example 1, except that the width of the channel 114 in the sensor of Comparative Example 2 is greater than 280 μm, which will cause the electrode / electrode wire to be too narrow, thus easily causing a circuit break. The trend of blood sugar changes after the sensor is implanted in a normal human body for 2 days is shown in FIG. Fig.40 As shown. Fig.40 It can be seen that since the channel width in the sensor is too wide, the electrode / electrode wire is too narrow, which will cause data "jumps" or "jitters" in the blood glucose test, affecting the stability of the test data.

[0227] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An analyte sensor, comprising a substrate, a working electrode, a reference electrode, a counter electrode and a sensing layer; the sensing layer is disposed on the working electrode; the working electrode, the reference electrode and the counter electrode are disposed on both sides of the substrate, respectively, and the two electrodes on the same side of the substrate are spatially separated by a channel; The width of the channel is 1 μm-280 μm; the length of the channel is 30 μm-10000 μm.

2. The analyte sensor according to claim 1, wherein The working electrode and the reference electrode are arranged on the first surface of the substrate, the working electrode and the reference electrode are spatially separated by a channel, and the counter electrode is arranged on the second surface of the substrate opposite to the first surface; or the working electrode and the counter electrode are arranged on the first surface of the substrate, the working electrode and the counter electrode are spatially separated by a channel, and the reference electrode is arranged on the second surface of the substrate opposite to the first surface; or the counter electrode and the reference electrode are arranged on the first surface of the substrate, the counter electrode and the reference electrode are spatially separated by a channel, and the working electrode is arranged on the second surface of the substrate opposite to the first surface. Preferably, the two electrodes located on the same side of the substrate are located on the same plane; Alternatively, the two electrode portions located on the same side of the substrate are located on the same plane.

3. The analyte sensor according to claim 1 or 2, wherein: The substrate comprises a front end, a middle end and a terminal end, and the front end, the middle end and the terminal end are sequentially connected and arranged; the substrate has an L shape, and the L shape comprises a first side and a second side, and a connection between the first side and the second side forms an angle, and the angle is 45°-135°; the front end is located on the first side and at a non-connected end of the first side, the terminal end is located on the second side and at a non-connected end of the second side, and the middle end is located on the first side and the second side, and at a connected end of the first side and a connected end of the second side.

4. The analyte sensor according to any one of claims 1 to 3, wherein: The working electrode comprises a working electrode layer, a working electrode wire and a working electrode contact, wherein the working electrode layer is connected to the working electrode contact via the working electrode wire; the working electrode layer is located at the front end of the substrate, the working electrode wire is located at the middle end of the substrate, and the working electrode contact is located at the end of the substrate; or, the working electrode layer and the working electrode wire are located at the middle end of the substrate, and the working electrode contact is located at the end of the substrate; The reference electrode comprises a reference electrode layer, a reference electrode wire and a reference electrode contact, wherein the reference electrode layer is arranged on the reference electrode wire, and the reference electrode wire is connected to the reference electrode contact; the reference electrode layer is located at the front end of the substrate, the reference electrode wire is located at the front end and the middle end of the substrate, and the reference electrode contact is located at the end of the substrate; or, the reference electrode layer and the reference electrode wire are located at the middle end of the substrate, and the reference electrode contact is located at the end of the substrate; The counter electrode includes a counter electrode layer, a counter electrode wire and a counter electrode contact, wherein the counter electrode layer is connected to the counter electrode contact via the counter electrode wire; the counter electrode layer is located at the front end of the substrate, the counter electrode wire is located at the middle end of the substrate, and the counter electrode contact is located at the end of the substrate; or, the counter electrode layer and the counter electrode wire are located at the middle end of the substrate, and the counter electrode contact is located at the end of the substrate. Preferably, the working electrode mainly plays the role of reacting with blood glucose; the function of the reference electrode is to form a voltage loop with the working electrode to provide a guarantee for converting the blood glucose signal into an electrochemical signal, and the reference electrode plays the role of stabilizing the electric potential, so that the analyte sensor has the function and role of continuous and stable monitoring; the function of the counter electrode is to form a current closed loop with the working electrode to provide a guarantee for converting the blood glucose signal into an electrochemical signal.

5. The analyte sensor according to any one of claims 1 to 4, wherein: The working electrode comprises a working electrode layer, and a sensing layer is arranged on the working electrode layer. Preferably, the analyte that the sensing layer can monitor is blood glucose.

6. The analyte sensor according to any one of claims 1 to 5, wherein: The electrode layer of one electrode and the electrode wire of the other electrode of the two electrodes located on the same side of the substrate are spatially separated by a trench. Preferably, the width of the channel is fixed or gradually varying.

7. The analyte sensor according to any one of claims 1 to 6, wherein: The analyte sensor has an L-shape, wherein the L-shape includes a first side and a second side, and a connection between the first side and the second side forms an angle, and the angle is 45°-135°. Preferably, there are two contact areas and two electrode areas on the first surface of the analyte sensor, and there is one contact area and one electrode area on the second surface of the analyte sensor opposite to the first surface, the electrode area is arranged on the first side of the L-shaped sensor, and the contact area is arranged on the second side of the sensor.

8. The analyte sensor according to any one of claims 1 to 7, wherein: A protrusion structure is formed at the connection between the first side and the second side. Preferably, a protrusion structure is formed at the outer edge of the connection between the first side and the second side.

9. The analyte sensor according to any one of claims 1 to 8, wherein: The analyte sensor further comprises a dielectric layer, which is arranged on a substrate, an electrode or an electrode wire. The dielectric layer can play an insulating role and is used to protect the working electrode, the counter electrode and the reference electrode from being damaged. Preferably, the analyte sensor further comprises a protective layer, and the protective layer is arranged at the outermost layer of the sensor.

10. The analyte sensor according to any one of claims 1 to 9, wherein: The front end and part of the middle end of the analyte sensor are implanted in the body, a current loop is formed by using the working electrode and the counter electrode, and a voltage loop is formed by using the working electrode and the reference electrode, so that the sensing layer located on the working electrode generates an electrochemical signal after reacting with blood glucose, thereby achieving the purpose of monitoring blood glucose; Preferably, the implanted length of the analyte sensor is 1 mm-20 mm and the width is 0.05 mm-10 mm.

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