Microelectrode structure, manufacturing method thereof and sensor

Abstract

The invention discloses a microelectrode structure and a manufacturing method thereof and a sensor, the microelectrode structure comprises a flexible substrate and a microelectrode system arranged on the surface of the flexible substrate, the microelectrode system comprises a counter electrode, a working electrode and a reference electrode, and electrode units are horizontally laid on the upper surface and the lower surface of the flexible substrate. The electrode units on the upper surface and the lower surface of the flexible substrate respectively comprise at least one of a counter electrode, a working electrode and a reference electrode, the electrode units on the upper surface of the flexible substrate form a first microelectrode system, and the electrode units on the lower surface of the flexible substrate form a second microelectrode system; or the electrode units on the upper surface and the lower surface of the flexible substrate jointly form a third microelectrode system. The electrodes are manufactured on the front side and the back side of the flexible substrate to form one or two microelectrode systems, the area of the microelectrodes is maximized on the limited surface of the substrate, and the detection precision is improved; double-channel double-substance monitoring, double-channel single-substance monitoring or single-channel single-substance monitoring can be achieved, and functional diversity is achieved.

Description

Technical Field

[0001] The present invention relates to the field of sensor technology, and more specifically, to a microelectrode structure and a manufacturing method thereof and a sensor. Background Art

[0002] Electrochemical sensors have become the most common means for people to detect body fluid analytes, especially micro-implantable electrochemical biosensors, such as dynamic blood glucose sensors, lactate sensors, uric acid sensors, etc., which can realize continuous dynamic monitoring of the concentration of human body fluid analytes, provide people with reliable body fluid analyte concentration change data, and assist in the prevention and in vitro diagnosis of related diseases.

[0003] Microelectrodes are important structures of electrochemical sensors, which play a role in signal conversion and transmission. The working principle of electrochemical sensors is to apply sensitive substances that have a specific response to the target analyte to the surface of the microelectrode. The sensitive substance will react specifically when it comes into contact with the target analyte. The microelectrode converts the concentration change of the target analyte during the reaction into electrical signals such as resistance, current or potential and outputs them to the external circuit. Usually within a limited concentration range, the converted electrical signal is proportional to the concentration of the target analyte. By analyzing the value of the electrical signal, the qualitative or quantitative analysis of the concentration change of the target analyte can be achieved.

[0004] The microelectrode is an electrochemical system including a working electrode, a counter electrode and a reference electrode, wherein the counter electrode and the working electrode form a polarization loop, which plays the role of transmitting electrons; the working electrode and the reference electrode form a measurement loop, which is used to test the electrochemical reaction process; the reference electrode potential is stable and known, and the electrode polarization and other voltage drops are basically negligible. The potential of the working electrode can be more easily measured by the reference electrode, so as to more accurately calculate the concentration of the analyte. The surface area of ​​the microelectrode determines the accuracy of the electrochemical sensor in detecting the target signal. The larger the surface area of ​​the microelectrode, the larger the contact area between the electrochemical sensor and the target analyte, the stronger the target signal, and the higher the detection accuracy. However, the overall volume of the electrochemical sensor should be kept as small as possible to meet the non-sensing requirements of implantation in the human body and improve the user's acceptability. Therefore, how to make a large-area microelectrode on the limited surface of the substrate is a technical problem that needs to be solved by those skilled in the art. Summary of the invention

[0005] In view of the shortcomings of the prior art, the present invention innovatively provides a microelectrode structure, a manufacturing method thereof, and a sensor, wherein electrodes are manufactured on both the front and back sides of a flexible substrate to form one or two microelectrode systems, thereby maximizing the area of ​​the microelectrode system on a limited flexible substrate surface, thereby improving the detection sensitivity and the detection accuracy of the sensor; dual-channel dual-substance monitoring, dual-channel single-substance monitoring, or single-channel single-substance monitoring can be realized, thereby achieving functional diversity.

[0006] To achieve the above technical objectives, a first aspect of the present invention provides a microelectrode structure, including a flexible substrate and a microelectrode system disposed on the surface of the flexible substrate.

[0007] The microelectrode system includes three electrode units, namely a counter electrode, a working electrode, and a reference electrode.

[0008] Electrode units are provided on both the upper surface and the lower surface of the flexible substrate. The electrode units on the upper surface of the flexible substrate include at least one of the counter electrode, the working electrode, and the reference electrode, and the electrode units on the upper surface of the flexible substrate are horizontally tiled and distributed on the upper surface. The electrode units on the lower surface of the flexible substrate include at least one of the counter electrode, the working electrode, and the reference electrode, and the electrode units on the lower surface of the flexible substrate are horizontally tiled and distributed on the lower surface.

[0009] The electrode units on the upper surface of the flexible substrate constitute a first microelectrode system, and the electrode units on the lower surface of the flexible substrate constitute a second microelectrode system. The first microelectrode system and the second microelectrode system are used to monitor the same substance or different substances.

[0010] Further, the counter electrode of the first microelectrode system and the counter electrode of the second microelectrode system are symmetrically disposed with respect to the flexible substrate. The working electrode of the first microelectrode system and the working electrode of the second microelectrode system are symmetrically disposed with respect to the flexible substrate. The reference electrode of the first microelectrode system and the reference electrode of the second microelectrode system are symmetrically disposed with respect to the flexible substrate.

[0011] Further, when the electrode units on the upper surface of the flexible substrate and the electrode units on the lower surface of the flexible substrate together constitute a third microelectrode system,

[0012] The number of electrode units on the upper and lower surfaces of the flexible substrate is 3. One of the electrode units on the upper and lower surfaces of the flexible substrate is a counter electrode, and the electrode units on the other surface are a working electrode and a reference electrode.

[0013] Alternatively, the number of electrode units on the upper and lower surfaces of the flexible substrate is 4 - 6. Counter electrodes are provided on both the upper and lower surfaces of the flexible substrate, as well as at least one working electrode and reference electrode. The similar electrode units on the upper and lower surfaces of the flexible substrate are connected to each other.

[0014] Further, in the first microelectrode system, the second microelectrode system, and the third microelectrode system, the total area of the counter electrodes > the total area of the working electrodes > the total area of the reference electrodes.

[0015] Further, the microelectrode structure further includes an electrical connection portion and a lead provided on the surface of the flexible substrate. The electrical connection portions are provided in one-to-one correspondence with the electrode units, and the leads correspondingly connect the electrode units to the corresponding electrical connection portions.

[0016] Further, a biosensitive material layer is provided on the surface of the working electrode facing away from the flexible substrate;

[0017] A first biofunctional layer is provided on the upper surface of the flexible substrate, and the first biofunctional layer covers the electrode units and the biosensitive material layer on the upper surface of the flexible substrate;

[0018] A second biofunctional layer is provided on the lower surface of the flexible substrate, and the second biofunctional layer covers the electrode units and the biosensitive material layer on the lower surface of the flexible substrate.

[0019] Further, the biosensitive material components included in the biosensitive material layers on the surfaces of the working electrodes of the first microelectrode system and the second microelectrode system are the same or different.

[0020] A second aspect of the present invention provides a method for manufacturing a microelectrode structure, and the manufacturing method includes:

[0021] Providing a flexible substrate;

[0022] Manufacturing corresponding electrode units on the upper surface and the lower surface of the flexible substrate. Among them, the electrode units on the upper surface of the flexible substrate include at least one of a counter electrode, a working electrode, and a reference electrode, and the electrode units on the lower surface of the flexible substrate include at least one of a counter electrode, a working electrode, and a reference electrode.

[0023] Further, the manufacturing of the corresponding electrode units on the upper surface and the lower surface of the flexible substrate specifically includes:

[0024] Providing a rigid substrate, manufacturing a temporary bonding layer on the rigid substrate, and attaching the flexible substrate to the temporary bonding layer;

[0025] Manufacturing the electrode units on one side on the surface of the flexible substrate facing away from the rigid substrate;

[0026] Separating the flexible substrate, the temporary bonding layer, and the rigid substrate, manufacturing a temporary bonding layer on the rigid substrate again, flipping the flexible substrate and the electrode units thereon, and attaching the side of the flexible substrate provided with the electrode units to the temporary bonding layer on the rigid substrate;

[0027] Manufacturing the electrode units on the other side on the surface of the flexible substrate facing away from the rigid substrate;

[0028] Separate the flexible substrate, the electrode units on the flexible substrate, the temporary bonding layer, and the rigid substrate.

[0029] Further, the reference electrode includes a bottom electrode and a chlorinated layer provided on the surface of the bottom electrode facing away from the flexible substrate.

[0030] Further, reference electrodes are provided on both the upper and lower surfaces of the flexible substrate. The reference electrode includes a bottom electrode and a chlorinated layer provided on the surface of the bottom electrode facing away from the flexible substrate.

[0031] Fabricating corresponding electrode units on the upper and lower surfaces of the flexible substrate specifically includes:

[0032] Provide a rigid substrate, fabricate a layer of temporary bonding layer on the rigid substrate, and attach the flexible substrate to the temporary bonding layer.

[0033] Fabricate the bottom electrode of one of the reference electrodes and the remaining electrode units on the same side of the reference electrode on the surface of the flexible substrate facing away from the rigid substrate.

[0034] Separate the flexible substrate, the temporary bonding layer, and the rigid substrate. Then, fabricate a layer of temporary bonding layer on the rigid substrate, flip the flexible substrate and the electrode units thereon, and attach the side of the flexible substrate with the electrode units to the temporary bonding layer on the rigid substrate.

[0035] Fabricate the bottom electrode of the other reference electrode and the remaining electrode units on the same side of the reference electrode on the surface of the flexible substrate facing away from the rigid substrate.

[0036] Separate the flexible substrate, the electrode units on the flexible substrate, the temporary bonding layer, and the rigid substrate.

[0037] Fabricate the chlorinated layer on the surfaces of the two bottom electrodes facing away from the rigid substrate.

[0038] Further, the chlorinated layer is formed by depositing silver on the surface of the bottom electrode facing away from the flexible substrate and converting part of the silver into silver chloride.

[0039] Further, the manufacturing method further includes:

[0040] Fabricate electrical connection parts corresponding to the electrode units one by one on the surface of the flexible substrate and leads for connecting the electrical connection parts to the electrode units one by one.

[0041] Further, the manufacturing method further includes:

[0042] After fabricating corresponding electrode units on the upper and lower surfaces of the flexible substrate,

[0043] a bio-sensitive material layer is fabricated on the surface of the working electrode facing away from the flexible substrate,

[0044] a first bio-functional layer is fabricated on the upper surface of the flexible substrate, and the first bio-functional layer covers the electrode unit on the upper surface of the flexible substrate and the bio-sensitive material layer; a second bio-functional layer is fabricated on the lower surface of the flexible substrate, and the second bio-functional layer covers the electrode unit on the lower surface of the flexible substrate and the bio-sensitive material layer.

[0045] Furthermore, when the electrode units on the upper surface of the flexible substrate form a first microelectrode system and the electrode units on the lower surface of the flexible substrate form a second microelectrode system, the bio-sensitive material components included in the bio-sensitive material layers on the surfaces of the working electrodes of the first microelectrode system and the second microelectrode system are the same or different.

[0046] Furthermore, the material of the temporary bonding layer is selected from organosilicon rubber or acrylic materials, and the viscosity of the temporary bonding layer is eliminated by means of light irradiation or heating.

[0047] The third aspect of the present invention provides a sensor, including the microelectrode structure described in the first aspect above or the microelectrode structure fabricated by the manufacturing method of the microelectrode structure described in the second aspect above.

[0048] The beneficial effects of the present invention are as follows:

[0049] The microelectrode structure of the present invention fabricates electrodes on both the front and back sides of the flexible substrate, thereby forming one or two microelectrode systems, maximizing the area of the microelectrode system on the limited surface of the flexible substrate, improving the detection sensitivity, and enhancing the detection accuracy of the sensor; it can achieve dual-channel dual-substance monitoring, dual-channel single-substance monitoring, or single-channel single-substance monitoring, realizing the diversity of functions. Description of the Drawings

[0050] Figure 1 is the front top view of the microelectrode structure of the first embodiment of the present invention.

[0051] Figure 2 is the back top view of the microelectrode structure of the first embodiment of the present invention.

[0052] Figure 3 is the longitudinal sectional view of the microelectrode structure of the first embodiment of the present invention (sectioned along the Figure 1 direction A-A in

[0053] Figure 4It is a front top view of the microelectrode structure according to the second embodiment of the present invention.

[0054] Figure 5 It is a back top view of the microelectrode structure according to the second embodiment of the present invention.

[0055] Figure 6 It is a longitudinal sectional view of the microelectrode structure according to the second embodiment of the present invention.

[0056] Figure 7 It is a longitudinal sectional view of the microelectrode structure according to the third embodiment of the present invention.

[0057] Figure 8 It is a longitudinal sectional view of the microelectrode structure according to the fourth embodiment of the present invention.

[0058] Figure 9 It is a longitudinal sectional view of the microelectrode structure according to the fifth embodiment of the present invention.

[0059] Figure 10 It is a longitudinal sectional view of the microelectrode structure according to the sixth embodiment of the present invention.

[0060] Figure 11 It is a longitudinal sectional view of the microelectrode structure according to the seventh embodiment of the present invention.

[0061] Figure 12 It is a longitudinal sectional view of the microelectrode structure according to the eighth embodiment of the present invention.

[0062] Figure 13 It is a flowchart of the manufacturing method of the microelectrode structure according to the embodiment of the present invention.

[0063] Figure 14 It is a specific flowchart of step S2 according to the embodiment of the present invention.

[0064] Figure 15 It is a specific flowchart of step S2 according to another embodiment of the present invention.

[0065] Figure 16 It is a manufacturing flowchart of the microelectrode structure according to the seventh embodiment of the present invention.

[0066] Figure 17 It is another manufacturing flowchart of the microelectrode structure according to the seventh embodiment of the present invention.

[0067] Figure 18 It is a manufacturing flowchart of the microelectrode structure according to the eighth embodiment of the present invention.

[0068] In the figure,

[0069] 1. Flexible substrate; 2. Counter electrode; 3. Working electrode; 4. Reference electrode; 41. Bottom electrode; 42. Chloride layer; 42'. Metallic silver layer; 5. Electrical connection part; 6. Lead wire; 7. Biosensitive material layer; 81. First biological function layer; 82. Second biological function layer; 9. Rigid substrate; 10. Temporary bonding layer; 11. First microelectrode system; 22. Second microelectrode system; 33. Third microelectrode system. Detailed implementation mode

[0070] The following combines the accompanying drawings of the specification to give a detailed explanation and description of the microelectrode structure, its manufacturing method and the sensor provided by the present invention.

[0071] This embodiment specifically discloses a microelectrode structure, as Figure 1-10 shown, including a flexible substrate 1 and a microelectrode system disposed on the surface of the flexible substrate 1. The microelectrode system includes three electrode units, namely a counter electrode 2, a working electrode 3 and a reference electrode 4. Electrode units are provided on both the upper surface and the lower surface of the flexible substrate 1. The electrode units on the upper surface of the flexible substrate 1 include at least one of the counter electrode 2, the working electrode 3 and the reference electrode 4, and the electrode units on the upper surface of the flexible substrate 1 are horizontally tiled and distributed on the upper surface. The electrode units on the lower surface of the flexible substrate 1 include at least one of the counter electrode 2, the working electrode 3 and the reference electrode 4, and the electrode units on the lower surface of the flexible substrate 1 are horizontally tiled and distributed on the lower surface. 1 to 3 electrode units can be provided on the upper surface of the flexible substrate 1, and 1 to 3 electrode units can be provided on the lower surface of the flexible substrate 1. When multiple electrode units are provided on the same surface, the types of the electrode units are different.

[0072] In some embodiments, as Figure 1-3 shown, the electrode units on the upper surface of the flexible substrate 1 constitute a first microelectrode system 11, the electrode units on the lower surface of the flexible substrate 1 constitute a second microelectrode system 22, the 3 electrode units on the upper surface of the flexible substrate 1 are the counter electrode 2, the working electrode 3 and the reference electrode 4, and the 3 electrode units on the lower surface of the flexible substrate 1 are the counter electrode 2, the working electrode 3 and the reference electrode 4. The positions and areas of the same type of electrode units on the upper and lower surfaces of the flexible substrate 1 can be the same or different. The same type of electrode units on the upper and lower surfaces of the flexible substrate 1 can be arranged back to back, or can be staggered or partially staggered, and the positions and areas of the respective electrode units can be set according to the monitoring needs.

[0073] The first microelectrode system 11 and the second microelectrode system 22 are used to monitor the same substance or different substances. When the first microelectrode system 11 and the second microelectrode system 22 monitor the same substance, the microelectrode structure can perform dual-channel monitoring on the same target analyte. The monitoring information of the first microelectrode system 11 and the second microelectrode system 22 can achieve complementary correction or redundant monitoring, so as to obtain more accurate monitoring data. Even if one of the microelectrode systems is damaged or malfunctioning, the other microelectrode system can still perform the monitoring function, making the microelectrode structure more reliable and having a longer service life. When the first microelectrode system 11 and the second microelectrode system 22 are used to monitor different substances, two different target analytes can be monitored, realizing dual-substance and dual-channel monitoring, and the monitored information is richer and more practical.

[0074] Preferably, the counter electrode 2 of the first microelectrode system 11 and the counter electrode 2 of the second microelectrode system 22 are symmetrically arranged with respect to the flexible substrate 1. The working electrode 3 of the first microelectrode system 11 and the working electrode 3 of the second microelectrode system 22 are symmetrically arranged with respect to the flexible substrate 1. The reference electrode 4 of the first microelectrode system 11 and the reference electrode 4 of the second microelectrode system 22 are symmetrically arranged with respect to the flexible substrate 1. That is, the same type of electrode units are arranged back-to-back on the flexible substrate 1 and have the same area, so that when the two microelectrode systems monitor the same substance, the target analyte at the same position can be monitored, making the monitored data more accurate and reducing errors.

[0075] In some embodiments, as Figure 4-10 shown, the electrode units on the upper surface of the flexible substrate 1 and the electrode units on the lower surface of the flexible substrate 1 together form a third microelectrode system 33, and the third microelectrode system 33 is used to achieve single-channel and single-substance monitoring.

[0076] Optionally, as Figure 4-6 shown, the number of electrode units on the upper and lower surfaces of the flexible substrate 1 is 3. One surface of the upper and lower surfaces of the flexible substrate 1 is provided with one electrode unit, and this electrode unit is the counter electrode 2. The other surface is provided with two electrode units, namely the working electrode 3 and the reference electrode 4. Compared with arranging the three electrode units of the microelectrode system on one side of the flexible substrate 1, in the embodiment of the present application, the three electrode units of the microelectrode system are distributed on the front and back sides of the flexible substrate 1, increasing the area of the microelectrode system. Moreover, the area of the counter electrode 2 in the third microelectrode system 33 is the largest, making the performance of the microelectrode structure reach the optimal state and improving the detection sensitivity.

[0077] Optionally, as Figure 7-10As shown, the number of electrode units on the upper and lower surfaces of the flexible substrate 1 is 4 to 6. Counter electrodes 2, at least one working electrode 3, and at least one reference electrode 4 are provided on both the upper and lower surfaces of the flexible substrate 1. The same type of electrode units on the upper and lower surfaces of the flexible substrate 1 are interconnected. The electrode units on the upper and lower surfaces of the flexible substrate 1 together form a microelectrode system to monitor a target analyte, achieving single-substance single-channel monitoring. In the embodiment of the present application, the same type of electrode units on the upper and lower surfaces of the flexible substrate 1 are connected as a whole to achieve the corresponding function, which is equivalent to distributing one of the electrode units of the microelectrode system on the upper and lower surfaces of the flexible substrate 1. Compared with arranging the three electrode units of the microelectrode system on one side of the flexible substrate 1, the area of this type of electrode unit is increased, and at the same time, the area limitation of this type of electrode unit on other electrode units is reduced, thereby correspondingly increasing the area of other electrode units and increasing the overall area of the microelectrode system. Moreover, counter electrodes 2 are provided on both the upper and lower surfaces of the flexible substrate 1, making the area of the counter electrode 2 in the third microelectrode system 33 the largest, enabling the performance of the microelectrode structure to reach the optimal level and improving the detection sensitivity.

[0078] As Figure 7 shown, the number of electrode units on the upper and lower surfaces of the flexible substrate 1 is 4. One electrode unit is provided on one side of the flexible substrate 1, and this electrode unit is the counter electrode 2; three electrode units are provided on the other side of the flexible substrate 1, and the three electrode units are the counter electrode 2, the working electrode 3, and the reference electrode 4. The counter electrodes 2 on the upper and lower surfaces are interconnected as a whole. Compared with the prior art of arranging the three electrode units of the microelectrode system on one side of the flexible substrate 1, in the embodiment of the present application, the counter electrode 2 of the microelectrode system is distributed on the upper and lower surfaces of the flexible substrate 1, increasing the area of the counter electrode 2 and reducing the area limitation of the counter electrode 2 on the areas of the other two electrode units, thereby correspondingly increasing the areas of the other two electrode units and further increasing the overall area of the microelectrode system.

[0079] As Figure 8 shown, the number of electrode units on the upper and lower surfaces of the flexible substrate 1 is 4. Two electrode units are provided on the upper surface of the flexible substrate 1, which are the counter electrode 2 and the working electrode 3 respectively. Two electrode units are provided on the lower surface of the flexible substrate 1, which are the counter electrode 2 and the reference electrode 4 respectively. The counter electrodes 2 on the upper and lower surfaces are interconnected as a whole, that is, the counter electrode 2 of the microelectrode system is distributed on the upper and lower surfaces of the flexible substrate 1, and the remaining two electrode units are each distributed on one side of the flexible substrate 1, reducing the area limitation between the electrode units when three electrode units are arranged on one side. The areas of the three electrode units are all increased, increasing the overall area of the microelectrode system.

[0080] As Figure 9As shown, the number of electrode units on the upper and lower surfaces of the flexible substrate 1 is 5. Two electrode units are arranged on one side of the flexible substrate 1. One of the electrode units is the counter electrode 2, and the other electrode unit is either the working electrode 3 or the reference electrode 4. Three electrode units are arranged on the other side of the flexible substrate 1, which are the counter electrode 2, the working electrode 3, and the reference electrode 4 respectively. By distributing two of the electrode units of the microelectrode system on the upper and lower surfaces of the flexible substrate 1 respectively, the areas of these two electrode units are increased, and the area limitation of these two electrode units on the remaining one electrode unit is reduced. As a result, the area of the remaining one electrode unit is correspondingly increased, and the overall area of the microelectrode system is increased.

[0081] As Figure 10 shown, the number of electrode units on the upper and lower surfaces of the flexible substrate 1 is 6. Three electrode units are arranged on one side of the flexible substrate 1, which are the counter electrode 2, the working electrode 3, and the reference electrode 4 respectively. Three electrode units are arranged on the other side of the flexible substrate 1, which are the counter electrode 2, the working electrode 3, and the reference electrode 4 respectively. By electrically connecting the same type of electrode units on the upper and lower surfaces of the flexible substrate 1, compared with arranging three electrode units of the microelectrode system on one side of the flexible substrate 1, the area of each type of electrode unit in this embodiment of the present application can be doubled, and thus the area of the microelectrode system is doubled. Preferably, the counter electrode 2, the working electrode 3, and the reference electrode 4 on the upper and lower surfaces of the flexible substrate 1 are symmetrically arranged with respect to the flexible substrate 1 one by one, and the two working electrodes 3 monitor the target analyte at the same position, making the monitoring result more accurate.

[0082] Preferably, the total area of the counter electrode 2 > the total area of the working electrode 3 > the total area of the reference electrode 4 in the first microelectrode system 11, the second microelectrode system 22, and the third microelectrode system 33, so that the performance of the microelectrode structure reaches the optimal under the condition of limited substrate area, and the detection sensitivity is improved.

[0083] In summary, compared with the prior art of fabricating microelectrodes on one side of the flexible substrate 1, the present application fabricates electrodes on both the front and back sides of the flexible substrate 1, which is equivalent to doubling the available area for fabricating the microelectrode system. As a result, the area of the fabricated microelectrode system can be increased by up to one time at most, achieving the maximization of the area of the microelectrode system on the limited flexible substrate surface, improving the detection sensitivity, and enhancing the detection accuracy of the sensor. Moreover, the flexibility of the microelectrode system design is increased, and the diversity and multi-functional design of the microelectrode system can be realized.

[0084] This application does not limit the specific product type of the sensor to which the microelectrode structure is applied. For example, in some embodiments, the microelectrode structure is applied to an electrochemical biosensor, and the surface of the working electrode 3 thereof is coated with a biosensitive material layer 7 (the biosensitive material is, for example, an enzyme, an antibody, or a nucleic acid, etc.), so that the electrochemical biosensor can realize the biological monitoring function of the target analyte (such as monitoring blood sugar, blood ketones, lactic acid, or uric acid, etc.). For example, in some embodiments, the microelectrode structure is applied to an electrochemical sensor, and the surface of the working electrode 3 thereof is coated with a chemically sensitive material layer, so that the electrochemical sensor can realize the chemical monitoring function of the target analyte (such as monitoring pH, ammonia, oxygen saturation, etc.). For example, in some embodiments, the microelectrode structure is applied to an electrochemical sensor, and the working electrode 3 thereof is made of a specific material or doped with a specific component, so that the working electrode 3 can directly react electrochemically with a certain component of the target analyte and convert it into a corresponding electrical signal. In these embodiments, the surface of the working electrode 3 may not need to be provided with a chemically sensitive material layer.

[0085] Optionally, the flexible substrate 1 can be made of materials such as polyimide film, polymethyl methacrylate film, polyethylene terephthalate film, polyethylene naphthalate film, etc., so that the microelectrode structure is flexible and bendable, and can be implanted in the body to meet the need for non-sensing implantation in the human body and improve user acceptability.

[0086] Optionally, the shape of the counter electrode 2, the working electrode 3 and the reference electrode 4 is one of a rectangle, a circle, an ellipse, an interdigitated shape, a regular polygon or an irregular polygon, which is not specifically limited in the present application.

[0087] In this embodiment, the reference electrode 4 includes a bottom electrode 41 and a chloride layer 42 on the surface of the bottom electrode 41 facing away from the flexible substrate 1, and the chloride layer 42 is formed by depositing silver on the surface of the bottom electrode 41 facing away from the flexible substrate 1 and converting part of the silver into silver chloride. Preferably, the ratio of silver to silver chloride in the chloride layer 42 is 1:1.

[0088] Optionally, the material of the bottom electrode 41 of the counter electrode 2, the working electrode 3 and the reference electrode 4 is one of chromium, gold or platinum. Preferably, the material of the bottom electrode 41 of the counter electrode 2, the working electrode 3 and the reference electrode 4 is the same and can be manufactured at the same time.

[0089] Optionally, the counter electrode 2, the working electrode 3, and the bottom electrode 41 of the reference electrode 4 are formed by first depositing a metal layer on the flexible substrate 1 using photolithography technology and then patterning. The method of depositing the metal layer on the flexible substrate 1 is one of electroplating, evaporation or sputtering, preferably sputtering. The patterning method is one of dry etching, wet etching or metal stripping, preferably wet etching.

[0090] Optionally, the method for depositing silver on the surface of the bottom electrode 41 is one of sputtering, electroplating or electroless plating, and the method for converting silver into silver chloride is one of electro-conversion or chemical conversion, preferably chemical conversion. The conversion solution used in chemical conversion is FeCl 3 solution, KCl solution or NaClO solution, and the concentration of the conversion solution is 0.1 - 3 mol / L.

[0091] In some embodiments, as Figure 1 , 2 , 4 and 5 show, the microelectrode structure further includes an electrical connection part 5 and a lead 6 arranged on the surface of the flexible substrate 1. The electrical connection part 5 is arranged corresponding to each electrode unit, and the lead 6 correspondingly connects the electrode unit with the corresponding electrical connection part 5. The electrical connection part 5 is used to connect the microelectrode structure with an external circuit.

[0092] When the same type of electrode units are arranged on the upper and lower surfaces of the flexible substrate 1, the electrical connection parts 5 corresponding to the two same type of electrode units can be electrically connected, so as to realize the mutual connection of the same type of electrode units.

[0093] The materials of the lead 6 and the electrical connection part 5 are one of chromium, gold or platinum. Preferably, the lead 6 and the electrical connection part 5 are made of the same material and can be fabricated simultaneously. The electrical connection part 5 and the lead 6 are formed on the flexible substrate 1 by first depositing a metal layer and then patterning using photolithography technology. The method for depositing the metal layer on the substrate 1 is one of electroplating, evaporation plating or sputtering, preferably sputtering, and the patterning method is one of dry etching, wet etching or lift-off, preferably wet etching. More preferably, the materials of the lead 6 and the electrical connection part 5 are the same as those of the bottom electrode 41 of the counter electrode 2, the working electrode 3 and the reference electrode 4, and can be fabricated simultaneously.

[0094] There are intervals between the electrode units, between the leads 6 and between the electrical connection parts 5 on the same surface of the flexible substrate 1. The arrangement of the leads 6 and the electrical connection parts 5 will limit the area of the electrode units. When the electrode units on the upper and lower surfaces of the flexible substrate 1 in the present application jointly form the third microelectrode system 33, one or two electrode units can be arranged on one or both surfaces of the flexible substrate 1, and the corresponding number of leads 6 and electrical connection parts 5 is reduced, which can avoid the limitation of the area of the corresponding electrode units by multiple leads 6, so that the area of the electrode units can be larger, thereby increasing the signal detection accuracy and reducing the manufacturing complexity.

[0095] In some embodiments, as Figure 11 and 12As shown, a biosensitive material layer 7 is provided on the surface of the working electrode 3 facing away from the flexible substrate 1; a first biofunctional layer 81 is provided on the upper surface of the flexible substrate 1, and the first biofunctional layer 81 covers the electrode units on the upper surface of the flexible substrate 1 and the biosensitive material layer 7; a second biofunctional layer 82 is provided on the lower surface of the flexible substrate 1, and the second biofunctional layer 82 covers the electrode units on the lower surface of the flexible substrate 1 and the biosensitive material layer 7. This microelectrode structure can be applied to an electrochemical microbial sensor.

[0096] The biosensitive material contained in the biosensitive material layer 7 is set according to the monitoring function, such as glucose oxidase for blood glucose monitoring, lactate dehydrogenase for lactate monitoring, and enzyme layers corresponding to other target analytes, such as biosensitive materials corresponding to uric acid and blood ketone.

[0097] The first biofunctional layer 81 and the second biofunctional layer 82 are used to protect the electrode units on the flexible substrate 1 and the biosensitive material layer 7, anti-interference (ensuring that only the target analyte enters the biosensitive material layer 7 and excluding the interference of other substances), and restricting the total amount and / or rate of the target analyte entering the biosensitive material layer 7. Optionally, the first biofunctional layer 81 and the second biofunctional layer 82 can adopt a selective permeable membrane with one or more layers stacked, and the specific number of layers of the selective permeable membrane is set according to actual monitoring needs. The first biofunctional layer 81 and the second biofunctional layer 82 may also include a hydrophilic polymer layer, and the hydrophilic polymer layer is provided on the surface of the selective permeable membrane away from the flexible substrate 1. The hydrophilic polymer layer has good biocompatibility and can be well compatible with biological tissues.

[0098] Optionally, the biosensitive material components included in the biosensitive material layer 7 on the surfaces of the working electrodes 3 of the first microelectrode system 11 and the second microelectrode system 22 are the same or different. When the biosensitive material components included in the biosensitive material layer 7 on the surfaces of the two working electrodes 3 are the same, dual-channel monitoring of the same target analyte can be achieved, and the two sets of collected data can be complementary and corrected, effectively preventing the phenomenon that the detection result of the target analyte is inaccurate due to the performance fluctuation of the single microelectrode system. At the same time, the damage of one microelectrode system does not affect the normal use of the other, improving the reliability of the microelectrode structure; when the biosensitive material components included in the biosensitive material layer 7 on the surfaces of the working electrodes 3 are different, the monitoring of two target analytes in body fluid can be achieved, that is, dual-channel and dual-substance monitoring. For example, the monitoring of blood glucose and uric acid can be achieved simultaneously, improving the practicability of the microelectrode structure; whether it is dual-channel single-substance or dual-channel dual-substance monitoring, since the microelectrode systems are fabricated on the front and back sides of the same substrate and then implanted into the body simultaneously, the monitoring data is more accurate. When performing dual-channel single-substance monitoring, the area of the microelectrodes is twice the area of the microelectrode system fabricated on one side of the same substrate area, and the detection is more accurate; when performing dual-channel dual-substance monitoring, the simultaneous monitoring of two target analytes makes the application of the microelectrode structure more extensive.

[0099] When the electrode units on the upper and lower surfaces of the flexible substrate 1 together form a microelectrode system (the third microelectrode system 33) and working electrodes 3 are provided on both, the microelectrode system is used for single-channel single-substance monitoring. The biosensitive material components included in the biosensitive material layer 7 on the surfaces of the two working electrodes 3 are the same, and the materials of the corresponding first biological functional layer 81 and second biological functional layer 82 are the same. When the first microelectrode system 11 and the second microelectrode system 22 are used to monitor the same substance, that is, when dual-channel single-substance monitoring is achieved, the biosensitive material components included in the biosensitive material layer 7 on the surfaces of the two working electrodes 3 are the same, and the materials of the corresponding first biological functional layer 81 and second biological functional layer 82 are the same. When the first microelectrode system 11 and the second microelectrode system 22 are used to monitor different substances, that is, when dual-channel dual-substance monitoring is achieved, the biosensitive material components included in the biosensitive material layer 7 on the surfaces of the two working electrodes 3 are different, and the materials of the corresponding first biological functional layer 81 and second biological functional layer 82 are different. When the electrode units on the upper and lower surfaces of the flexible substrate 1 together form the third microelectrode system 33 and only one side is provided with the working electrode 3, the materials of the first biological functional layer 81 and the second biological functional layer 82 are the same.

[0100] The microelectrode structure of the present application has the characteristics of good flexibility, small volume, high sensitivity, strong anti-interference ability, high accuracy, good biocompatibility, etc., and can achieve non-invasive and high-precision health monitoring of the human body.

[0101] The present application also provides a manufacturing method of a microelectrode structure, as Figure 13As shown, the manufacturing method specifically includes:

[0102] S1. Provide a flexible substrate 1; the flexible substrate 1 can be made of materials such as polyimide film, polymethyl methacrylate film, polyethylene terephthalate film, polyethylene naphthalate film, etc.

[0103] S2. Fabricate corresponding electrode units on the upper surface and the lower surface of the flexible substrate 1. Among them, the electrode units on the upper surface of the flexible substrate 1 include at least one of the counter electrode 2, the working electrode 3, and the reference electrode 4, and the electrode units on the lower surface of the flexible substrate 1 include at least one of the counter electrode 2, the working electrode 3, and the reference electrode 4. The electrode units on the upper surface of the flexible substrate 1 form a microelectrode system, and the electrode units on the lower surface of the flexible substrate 1 form a microelectrode system; or the electrode units on the upper surface of the flexible substrate 1 and the electrode units on the lower surface of the flexible substrate 1 together form a microelectrode system.

[0104] In some embodiments, as Figure 14 shown, step S2 specifically includes:

[0105] S21. Provide a rigid substrate 9 and fabricate a temporary bonding layer 10 on the rigid substrate 9. ， Attach the flexible substrate 1 to the temporary bonding layer 10. The rigid substrate 9 is used to support the flexible substrate 1 to facilitate the subsequent fabrication of electrode units on the flexible substrate 1. The rigid substrate 9 can be made of materials such as silicon, glass, and ceramics. The material of the temporary bonding layer 10 is selected from organic silicone-based or acrylic-based materials and is used to adhere to the flexible substrate 1. The flexible substrate 1 is coated on top of the temporary bonding layer 10, and the viscosity of the temporary bonding layer 10 can be eliminated by light irradiation or heating to facilitate the separation of the flexible substrate 1 from the rigid substrate 9.

[0106] S22. Fabricate the electrode units on one side on the surface of the flexible substrate 1 facing away from the rigid substrate 9.

[0107] The reference electrode 4 includes a bottom electrode 41 and a chloride layer 42 provided on the surface of the bottom electrode 41 facing away from the flexible substrate 1. The chloride layer 42 is formed by depositing silver on the surface of the bottom electrode 41 facing away from the flexible substrate 1 and converting part of the silver into silver chloride.

[0108] If the electrode units on this side only include the reference electrode 4, the bottom electrode 41 of the reference electrode 4 can be fabricated first on the surface of the flexible substrate 1 facing away from the rigid substrate 9 (i.e., the upper surface of the flexible substrate 1 at this time), and then a metal silver layer 42' is deposited on the upper surface of the bottom electrode 41 of the reference electrode 4, and part of the silver in the metal silver layer 42' is converted into silver chloride (for example, by immersing the entire structure in a chloride solution) to form the chloride layer 42.

[0109] When two or three electrode units are provided on this surface and one of them is the reference electrode 4, the bottom electrode 41 of the reference electrode 4 and other electrode units can be fabricated on the surface of the flexible substrate 1 facing away from the rigid substrate 9 (i.e., the upper surface of the flexible substrate 1 at this time), and then a silver metal layer 42' is deposited on the bottom electrode 41 of the reference electrode 4, and part of the silver in the silver metal layer 42' is converted into silver chloride (for example, by immersing the entire structure in a chloride solution), forming a chloride layer 42.

[0110] If the reference electrode 4 is not provided on this surface, the counter electrode 2 and / or the working electrode 3 are fabricated on the surface of the flexible substrate 1 facing away from the rigid substrate 9 (i.e., the upper surface of the flexible substrate 1 at this time).

[0111] S23. Separate the flexible substrate 1, the temporary bonding layer 10, and the rigid substrate 9, eliminate the adhesiveness of the temporary bonding layer 10 in the form of light irradiation or heating to achieve the separation of the flexible substrate 1 and the rigid substrate 9, then fabricate a new layer of temporary bonding layer 10 on the upper surface of the rigid substrate 9, flip the flexible substrate 1 and the electrode units thereon, and attach the surface of the flexible substrate 1 with the electrode units to the temporary bonding layer 10 on the rigid substrate 9, so that the electrode units and the lower surface of the flexible substrate 1 at this time are bonded to the temporary bonding layer 10.

[0112] S24. Fabricate the electrode units on the other surface on the surface of the flexible substrate 1 facing away from the rigid substrate 9, and the specific fabrication method of the electrode units is the same as that in step S22 above.

[0113] S25. Separate the flexible substrate 1, the electrode units on the flexible substrate 1, the temporary bonding layer 10, and the rigid substrate 9. Specifically, eliminate the adhesiveness of the temporary bonding layer 10 in the form of light irradiation or heating to achieve the separation of the flexible substrate 1 and the electrode units from the rigid substrate 9.

[0114] In some embodiments, reference electrodes 4 are provided on both the upper and lower surfaces of the flexible substrate 1. At this time, as Figure 15 shown, step S2 specifically includes:

[0115] S21'. Provide a rigid substrate 9, fabricate a layer of temporary bonding layer 10 on the rigid substrate 9, and attach the flexible substrate 1 to the temporary bonding layer 10.

[0116] S22': Fabricate the bottom electrode 41 of one of the reference electrodes 4 and the remaining electrode units on the same side of the reference electrode 4 on the surface of the flexible substrate 1 facing away from the rigid substrate 9. If only the reference electrode 4 is provided on this surface, fabricate the bottom electrode 41 of the reference electrode 4 on the upper surface of the flexible substrate 1 at this time, and then deposit a silver metal layer 42' on the bottom electrode 41 of the reference electrode 4. If the counter electrode 2 and / or the working electrode 3 are also provided on this surface, fabricate the bottom electrode 41 of the reference electrode 4 and other electrodes on the upper surface of the flexible substrate 1 at this time, and then deposit a silver metal layer 42' on the bottom electrode 41 of the reference electrode 4.

[0117] S23': Separate the flexible substrate 1, the temporary bonding layer 10 and the rigid substrate 9. Specifically, eliminate the adhesiveness of the temporary bonding layer 10 by means of light irradiation or heating to achieve the separation of the flexible substrate 1 and the rigid substrate 9; then fabricate a layer of temporary bonding layer 10 on the rigid substrate 9, flip the flexible substrate 1 and the electrode units thereon, and attach the side of the flexible substrate 1 with the electrode units to the temporary bonding layer 10 on the rigid substrate 9, so that the electrode units and the lower surface of the flexible substrate 1 at this time adhere to the temporary bonding layer 10.

[0118] S24': Fabricate the bottom electrode 41 of the other reference electrode 4 and the remaining electrode units on the same side of the reference electrode 4 on the surface of the flexible substrate 1 facing away from the rigid substrate 9. The specific fabrication method of the electrode units is the same as that in step S22'.

[0119] S25': Separate the flexible substrate 1, the electrode units on the flexible substrate 1, the temporary bonding layer 10 and the rigid substrate 9. Eliminate the adhesiveness of the temporary bonding layer 10 by means of light irradiation or heating to achieve the separation of the flexible substrate 1 and the electrode units from the rigid substrate 9.

[0120] S26': Fabricate the chloride layer 42 on the surfaces of the two bottom electrodes 41 facing away from the rigid substrate 9. At this time, the surfaces of the two bottom electrodes 41 far from the rigid substrate 9 are both silver metal layers 42'. Part of the silver in the silver metal layers 42' on both sides of the flexible substrate 1 can be converted into silver chloride simultaneously (for example, immerse the flexible substrate 1 and the electrode units on its front and back sides in a chloride solution at the same time) to form the chloride layer 42.

[0121] Optionally, the bottom electrodes 41 of the counter electrode 2, the working electrode 3 and the reference electrode 4 are all formed on the flexible substrate 1 by first depositing a metal layer and then patterning using photolithography technology. The method of depositing the metal layer on the flexible substrate is one of electroplating, evaporation plating or sputtering, preferably sputtering. The patterning method is one of dry etching, wet etching or lift-off, preferably wet etching.

[0122] Optionally, the method for depositing silver on the surface of the bottom electrode 41 is one of sputtering, electroplating or electroless plating, and the method for converting silver into silver chloride is one of electro-conversion or chemical conversion, preferably chemical conversion. The conversion solution used in chemical conversion is FeCl 3 solution, KCl solution or NaClO solution, and the concentration of the conversion solution is 0.1 - 3 mol / L.

[0123] In some embodiments, the manufacturing method further includes:

[0124] Fabricating electrical connection portions 5 corresponding to the electrode units one by one on the surface of the flexible substrate 1 and leads 6 for connecting the electrical connection portions 5 to the electrode units one by one. If the materials of the electrical connection portions 5 and leads 6 are the same as those of the bottom electrodes 41 of the counter electrode 2, working electrode 3 and reference electrode 4, the leads 6 and electrical connection portions 5 corresponding to the electrode units can be fabricated simultaneously when fabricating the bottom electrodes 41 of the counter electrode 2, working electrode 3 and reference electrode 4 in step S2. If the materials of the electrical connection portions 5 and leads 6 are different from those of the bottom electrodes 41 of the counter electrode 2, working electrode 3 and reference electrode 4, the leads 6 and electrical connection portions 5 corresponding to the electrode units can be fabricated after fabricating the bottom electrodes 41 of the counter electrode 2, working electrode 3 and reference electrode 4 in step S2. Preferably, the materials of the electrical connection portions 5 and leads 6 are the same as those of the bottom electrodes 41 of the counter electrode 2, working electrode 3 and reference electrode 4, and the leads 6 and electrical connection portions 5 corresponding to the electrode units are fabricated simultaneously when fabricating the bottom electrodes 41 of the counter electrode 2, working electrode 3 and reference electrode 4 in step S2, and can be formed by first depositing a metal layer and then patterning using photolithography technology.

[0125] In some embodiments, the manufacturing method further includes:

[0126] S3. Fabricating a bio-sensitive material layer 7 on the surface of the working electrode 3 facing away from the flexible substrate 1, fabricating a first bio-functional layer 81 on the upper surface of the flexible substrate 1, and the first bio-functional layer 81 covers the electrode units on the upper surface of the flexible substrate 1 and the bio-sensitive material layer 7; fabricating a second bio-functional layer 82 on the lower surface of the flexible substrate 1, and the second bio-functional layer 82 covers the electrode units on the lower surface of the flexible substrate 1 and the bio-sensitive material layer 7. In this embodiment, the bio-sensitive material layer 7 is fabricated using film-forming processes such as drop coating, dip coating, spin coating, spray coating, etc., and the bio-sensitive material layer 7 can cover the surface of the flexible substrate 1 where the working electrode 3 is located and other electrode units on this surface. The first bio-functional layer 81 and the second bio-functional layer 82 can be formed using film-forming processes such as drop coating, dip coating, spin coating, spray coating, etc., and after the bio-sensitive material layer 7 is completed, the first bio-functional layer 81 and the second bio-functional layer 82 are fabricated.

[0127] Such as Figure 16As shown in the figure, it is a manufacturing flow chart of the microelectrode structure according to the seventh embodiment of the present application. Among them, the electrode units on the upper surface of the flexible substrate 1 constitute the first microelectrode system 11, and the electrode units on the lower surface of the flexible substrate 1 constitute the second microelectrode system 22. On one side of the flexible substrate 1, a counter electrode 2, a working electrode 3, and a reference electrode 4 are provided, and on the other side of the flexible substrate 1, a counter electrode 2, a working electrode 3, and a reference electrode 4 are provided. The manufacturing method specifically includes the following steps:

[0128] S1. Provide the flexible substrate 1.

[0129] S2. For the electrode units corresponding to the upper surface and the lower surface of the flexible substrate 1, specifically:

[0130] S21. Provide a rigid substrate 9. First, fabricate a temporary bonding layer 10 on the rigid substrate 9, and then laminate the flexible substrate 1 above the temporary bonding layer 10.

[0131] S22. Fabricate the bottom electrodes 41 of the counter electrode 2, the working electrode 3, and the reference electrode 4, as well as the leads 6 and the electrical connection parts 5 corresponding to the connection with the counter electrode 2, the working electrode 3, and the reference electrode 4 on the surface of the flexible substrate 1 facing away from the rigid substrate 9. Then deposit a silver metal layer 42' on the upper surface of the bottom electrode 41, and immerse the entire structure in a chloride solution to convert part of the silver in the silver metal layer 42' into silver chloride to form a chloride layer 42, obtaining the structure shown in Figure a.

[0132] S23. Eliminate the viscosity of the temporary bonding layer 10 in the form of light irradiation or heating, separate the flexible substrate 1, the temporary bonding layer 10, and the rigid substrate 9, and then fabricate a temporary bonding layer 10 on the rigid substrate 9. Flip the flexible substrate 1 and its electrode units thereon, and attach the side of the flexible substrate 1 with the electrode units to the temporary bonding layer 10 on the rigid substrate 9.

[0133] S24. Fabricate the bottom electrodes 41 of the counter electrode 2, the working electrode 3, and the reference electrode 4, as well as the leads 6 and the electrical connection parts 5 corresponding to the counter electrode 2, the working electrode 3, and the reference electrode 4 on the surface of the flexible substrate 1 facing away from the rigid substrate 9. Then deposit a silver metal layer 42' on the upper surface of the bottom electrode 41, and immerse the entire structure in a chloride solution to convert part of the silver in the silver metal layer 42' into silver chloride to form a chloride layer 42, obtaining the structure shown in Figure b.

[0134] S25. Eliminate the viscosity of the temporary bonding layer 10 in the form of light irradiation or heating, separate the flexible substrate 1, the electrode units on the flexible substrate 1, the temporary bonding layer 10, and the rigid substrate 9, obtaining the structure shown in Figure c.

[0135] S3. On the surfaces of the two working electrodes 3 facing away from the flexible substrate 1, a bio-sensitive material layer 7 is fabricated respectively. The bio-sensitive material components included in the two bio-sensitive material layers 7 can be the same or different; on the upper surface of the flexible substrate 1, a first bio-functional layer 81 is fabricated, and the first bio-functional layer 81 covers all the electrode units and the bio-sensitive material layer 7 on the upper surface of the flexible substrate 1; on the lower surface of the flexible substrate 1, a second bio-functional layer 82 is fabricated, and the second bio-functional layer 82 covers all the electrode units and the bio-sensitive material layer 7 on the lower surface of the flexible substrate 1. If the bio-sensitive material components included in the two bio-sensitive material layers 7 are the same, the materials of the first bio-functional layer 81 and the second bio-functional layer 82 are the same; if the bio-sensitive material components included in the two bio-sensitive material layers 7 are different, the materials of the first bio-functional layer 81 and the second bio-functional layer 82 are also different. Finally, the structure shown in Fig. d is obtained.

[0136] As Figure 17 shown, it is another manufacturing flow chart of the microelectrode structure according to the seventh embodiment of the present application. Among them, the electrode units on the upper surface of the flexible substrate 1 constitute the first microelectrode system 11, and the electrode units on the lower surface of the flexible substrate 1 constitute the second microelectrode system 22. On one side of the flexible substrate 1, a counter electrode 2, a working electrode 3, and a reference electrode 4 are provided, and on the other side of the flexible substrate 1, a counter electrode 2, a working electrode 3, and a reference electrode 4 are provided. The manufacturing method specifically includes the following steps;

[0137] S1. Provide a flexible substrate 1.

[0138] S2. Fabricate corresponding electrode units on the upper surface and the lower surface of the flexible substrate 1. Specifically:

[0139] S21’. Provide a rigid substrate 9. First, fabricate a temporary bonding layer 10 on the rigid substrate 9, and then laminate the flexible substrate 1 above the temporary bonding layer 10.

[0140] S22’. On the surface of the flexible substrate 1 facing away from the rigid substrate 9, fabricate the bottom electrodes 41 of the counter electrode 2, the working electrode 3, and the reference electrode 4, as well as the leads 6 and the electrical connection parts 5 corresponding to the counter electrode 2, the working electrode 3, and the reference electrode 4. Deposit a silver metal layer 42’ on the bottom electrode 41 of the reference electrode 4 to obtain the structure shown in Fig. a.

[0141] S23’. Eliminate the adhesiveness of the temporary bonding layer 10 in the form of light irradiation or heating, separate the flexible substrate 1, the temporary bonding layer 10, and the rigid substrate 9, then fabricate a temporary bonding layer 10 on the rigid substrate 9, flip the flexible substrate 1 and the electrode units thereon, and attach the side of the flexible substrate 1 with the electrode units to the temporary bonding layer 10 on the rigid substrate 9.

[0142] S24’. Fabricate the bottom electrodes 41 of the counter electrode 2, working electrode 3, and reference electrode 4, as well as the leads 6 and electrical connection parts 5 corresponding to the counter electrode 2, working electrode 3, and reference electrode 4, on the surface of the flexible substrate 1 facing away from the rigid substrate 9. Deposit a silver metal layer 42’ on top of the bottom electrode 41 of the reference electrode 4 to obtain the structure shown in Fig. b.

[0143] S25’. Eliminate the viscosity of the temporary bonding layer 10 by means of light irradiation or heating, and separate the flexible substrate 1, the electrode units on the flexible substrate 1, the temporary bonding layer 10, and the rigid substrate 9.

[0144] S26’. Fabricate the chloride layer 42 of the reference electrode 4 on the surfaces of the two bottom electrodes 41 facing away from the rigid substrate 9. At this time, the surfaces of the two bottom electrodes 41 far from the rigid substrate 9 are both silver metal layers 42’. Immerse the flexible substrate 1 and the electrode units on its front and back surfaces in the chloride solution at the same time, and convert part of the silver in the silver metal layers 42’ on both sides of the flexible substrate 1 into silver chloride to form the chloride layer 42, obtaining the structure shown in Fig. c.

[0145] S3. Fabricate the biocompatible material layers 7 on the surfaces of the two working electrodes 3 facing away from the flexible substrate 1. The biocompatible material components included in the two biocompatible material layers 7 can be the same or different; fabricate the first biofunctional layer 81 on the upper surface of the flexible substrate 1, and the first biofunctional layer 81 covers all the electrode units and biocompatible material layers 7 on the upper surface of the flexible substrate 1; fabricate the second biofunctional layer 82 on the lower surface of the flexible substrate 1, and the second biofunctional layer 82 covers all the electrode units and biocompatible material layers 7 on the lower surface of the flexible substrate 1. If the biocompatible material components included in the two biocompatible material layers 7 are the same, the materials of the first biofunctional layer 81 and the second biofunctional layer 82 are the same; if the biocompatible material components included in the two biocompatible material layers 7 are different, the materials of the first biofunctional layer 81 and the second biofunctional layer 82 are also different. Finally, obtain the structure shown in Fig. d.

[0146] As Figure 18 shown, it is a flowchart for fabricating the microelectrode structure according to the eighth embodiment of the present application. Among them, a counter electrode 2 is arranged on one side of the flexible substrate 1, and a working electrode 3 and a reference electrode 4 are arranged on the other side of the flexible substrate 1. The fabrication method specifically includes the following steps:

[0147] S1. Provide a flexible substrate 1.

[0148] S2. Fabricate the corresponding electrode units on the upper surface and the lower surface of the flexible substrate 1. Specifically:

[0149] S21. Provide a rigid substrate 9, first fabricate a layer of temporary bonding layer 10 on the rigid substrate 9, and then laminate the flexible substrate 1 above the temporary bonding layer 10.

[0150] S22. Fabricate the counter electrode 2, the lead 6 and the electrical connection part 5 correspondingly connected to the counter electrode 2 on the surface of the flexible substrate 1 facing away from the rigid substrate 9, obtaining the structure shown in Fig. a.

[0151] S23. Eliminate the viscosity of the temporary bonding layer 10 in the form of light irradiation or heating, separate the flexible substrate 1, the temporary bonding layer 10 and the rigid substrate 9, then fabricate a layer of temporary bonding layer 10 on the rigid substrate 9, flip the flexible substrate 1 and the counter electrode 2 thereon, and attach the side of the flexible substrate 1 with the counter electrode 2 to the temporary bonding layer 10 on the rigid substrate 9.

[0152] S24. Fabricate the working electrode 3, the bottom electrode 41 of the reference electrode 4 and the leads 6 and electrical connection parts 5 corresponding to the working electrode 3 and the reference electrode 4 on the surface of the flexible substrate 1 facing away from the rigid substrate 9, then deposit a silver metal layer 42' on the upper surface of the bottom electrode 41, and then immerse the whole structure in a chloride solution to convert part of the silver in the silver metal layer 42' into silver chloride to form a chloride layer 42, obtaining the structure shown in Fig. b.

[0153] S25. Eliminate the viscosity of the temporary bonding layer 10 in the form of light irradiation or heating, separate the flexible substrate 1, the electrode unit on the flexible substrate 1, the temporary bonding layer 10 and the rigid substrate 9, obtaining the structure shown in Fig. c.

[0154] S3. Fabricate the bio-sensitive material layer 7 on the surface of the working electrode 3 facing away from the flexible substrate 1, fabricate the first bio-functional layer 81 on the upper surface of the flexible substrate 1, and the first bio-functional layer 81 covers the working electrode 3, the reference electrode 4 and the bio-sensitive material layer 7 on the upper surface of the flexible substrate 1; fabricate the second bio-functional layer 82 on the lower surface of the flexible substrate 1, and the second bio-functional layer 82 covers the counter electrode 2 on the lower surface of the flexible substrate 1. The first bio-functional layer 81 and the second bio-functional layer 82 are made of the same material, obtaining the structure shown in Fig. d.

[0155] When fabricating the microelectrode structure of the eighth embodiment, if the working electrode 3 and the reference electrode 4 are fabricated first and then the counter electrode 2 is fabricated, step S22 is specifically: fabricate the bottom electrode 41 of the working electrode 3 and the reference electrode 4 and the leads 6 and electrical connection parts 5 correspondingly connected to the working electrode 3 and the reference electrode 4 on the surface of the flexible substrate 1 facing away from the rigid substrate 9, then deposit a silver metal layer 42' on the upper surface of the bottom electrode 41, and then immerse the whole structure in a chloride solution to convert part of the silver in the silver metal layer 42' into silver chloride to form a chloride layer 42. Then perform step S23.

[0156] The present application also provides a sensor, including the microelectrode structure described in the above embodiments or the microelectrode structure fabricated by the method for fabricating the microelectrode structure described in the above embodiments. The specific product type of the sensor is not limited. For example, it can be an electrochemical biosensor or an electrochemical sensor, etc. Among them, the electrochemical biosensor can be an implantable electrochemical biosensor for implanting into a living body, or an in vitro electrochemical biosensor for immersing in a solution containing a target analyte.

[0157] In the present application, electrode units are laid flat on both sides of the flexible substrate 1. While increasing the area of the microelectrode system, only the thickness of one layer of electrode units is increased, so that the volume of the entire microelectrode structure and the corresponding sensor is small, reducing the rejection reaction generated by the human body when implanted into the human body, meeting the requirement of being imperceptible when implanted into the human body, and improving the acceptability of users.

[0158] In the description of the present invention, it should be understood that the orientation or positional relationship indicated by the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as a limitation on the present invention.

[0159] In the present invention, unless otherwise clearly defined and limited, the terms "mounted", "connected", "connected to", "fixed", etc. should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or integrated; it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the communication inside two elements or the interaction relationship between two elements, unless otherwise clearly defined. For those of ordinary skill in the art, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0160] In the description of this specification, the descriptions referring to terms such as "this embodiment", "one embodiment", "some embodiments", "examples", "specific examples", or "some examples" etc. mean that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described may be combined in a suitable manner in any at least one embodiment or example. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments or examples described in this specification and the features of different embodiments or examples.

[0161] In addition, the terms "first" and "second" are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include at least one of such features. In the description of the present invention, the meaning of "a plurality" is at least two, such as two, three, etc., unless otherwise specifically and clearly defined.

[0162] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and simple improvements made to the substantial content of the present invention shall be included within the protection scope of the present invention.

Claims

1. A microelectrode structure, characterized in that: It comprises a flexible substrate (1) and a microelectrode system arranged on the surface of the flexible substrate (1). The microelectrode system comprises three electrode units, namely a counter electrode (2), a working electrode (3) and a reference electrode (4). The upper surface and the lower surface of the flexible substrate (1) are both provided with electrode units, the electrode units on the upper surface of the flexible substrate (1) include at least one of a counter electrode (2), a working electrode (3) and a reference electrode (4), the electrode units on the upper surface of the flexible substrate (1) are horizontally flatly distributed, the electrode units on the lower surface of the flexible substrate (1) include at least one of a counter electrode (2), a working electrode (3) and a reference electrode (4), the electrode units on the lower surface of the flexible substrate (1) are horizontally flatly distributed, The electrode units on the upper surface of the flexible substrate (1) constitute a first microelectrode system (11), and the electrode units on the lower surface of the flexible substrate (1) constitute a second microelectrode system (22), and the first microelectrode system (11) and the second microelectrode system (22) are used to monitor the same substance or different substances. Alternatively, the electrode units on the upper surface of the flexible substrate (1) and the electrode units on the lower surface of the flexible substrate (1) together constitute a third microelectrode system (33).

2. The microelectrode structure according to claim 1, characterized in that: The counter electrode (2) of the first microelectrode system (11) and the counter electrode (2) of the second microelectrode system (22) are symmetrically arranged with respect to the flexible substrate (1); the working electrode (3) of the first microelectrode system (11) and the working electrode (3) of the second microelectrode system (22) are symmetrically arranged with respect to the flexible substrate (1); and the reference electrode (4) of the first microelectrode system (11) and the reference electrode (4) of the second microelectrode system (22) are symmetrically arranged with respect to the flexible substrate (1).

3. The microelectrode structure according to claim 1, characterized in that: When the electrode units on the upper surface of the flexible substrate (1) and the electrode units on the lower surface of the flexible substrate (1) together form a third microelectrode system (33), The number of electrode units on the upper and lower surfaces of the flexible substrate (1) is three, the electrode unit on one of the upper and lower surfaces of the flexible substrate (1) is a counter electrode (2), and the electrode units on the other surface are a working electrode (3) and a reference electrode (4), Alternatively, the number of electrode units on the upper and lower surfaces of the flexible substrate (1) is 4 to 6, the upper and lower surfaces of the flexible substrate (1) are both provided with a counter electrode (2), and at least one working electrode (3) and a reference electrode (4), and the same type of electrode units on the upper and lower surfaces of the flexible substrate (1) are connected to each other.

4. The microelectrode structure according to any one of claims 1 to 3, characterized in that: The total area of ​​the counter electrode (2) in the first microelectrode system (11), the second microelectrode system (22) and the third microelectrode system (33)>the total area of ​​the working electrode (3)>the total area of ​​the reference electrode (4).

5. The microelectrode structure according to claim 1, characterized in that: The microelectrode structure further comprises an electrical connection portion (5) and a lead wire (6) arranged on the surface of the flexible substrate (1); the electrical connection portion (5) is arranged in a one-to-one correspondence with the electrode unit, and the lead wire (6) connects the electrode unit to the corresponding electrical connection portion (5).

6. The microelectrode structure according to claim 1, characterized in that: A biosensitive material layer (7) is provided on the surface of the working electrode (3) facing away from the flexible substrate (1); A first biofunctional layer (81) is provided on the upper surface of the flexible substrate (1), and the first biofunctional layer (81) covers the electrode unit and the biosensitive substance layer (7) on the upper surface of the flexible substrate (1); A second biofunctional layer (82) is provided on the lower surface of the flexible substrate (1), and the second biofunctional layer (82) covers the electrode unit and the biosensitive substance layer (7) on the lower surface of the flexible substrate (1).

7. The microelectrode structure according to claim 6, characterized in that: The biosensitive substance components contained in the biosensitive substance layer (7) on the surface of the working electrode (3) of the first microelectrode system (11) and the second microelectrode system (22) are the same or different.

8. A method for manufacturing a microelectrode structure according to any one of claims 1 to 7, characterized in that: The production method comprises: Providing a flexible substrate (1); Corresponding electrode units are manufactured on the upper surface and the lower surface of the flexible substrate (1), wherein the electrode unit on the upper surface of the flexible substrate (1) includes at least one of a counter electrode (2), a working electrode (3) and a reference electrode (4), and the electrode unit on the lower surface of the flexible substrate (1) includes at least one of a counter electrode (2), a working electrode (3) and a reference electrode (4).

9. The method for manufacturing a microelectrode structure according to claim 8, characterized in that: The manufacturing of corresponding electrode units on the upper surface and the lower surface of the flexible substrate (1) specifically includes: A rigid substrate (9) is provided, a temporary bonding layer (10) is made on the rigid substrate (9), and the flexible substrate (1) is attached to the temporary bonding layer (10). An electrode unit is fabricated on one side of the surface of the flexible substrate (1) facing away from the rigid substrate (9), The flexible substrate (1), the temporary bonding layer (10) and the rigid substrate (9) are separated, and a temporary bonding layer (10) is formed on the rigid substrate (9), the flexible substrate (1) and the electrode unit thereon are turned over, and a surface of the flexible substrate (1) provided with the electrode unit is attached to the temporary bonding layer (10) on the rigid substrate (9); An electrode unit is fabricated on the other side of the surface of the flexible substrate (1) facing away from the rigid substrate (9). The flexible substrate (1) and the electrode unit on the flexible substrate (1), the temporary bonding layer (10) and the rigid substrate (9) are separated.

10. The method for manufacturing a microelectrode structure according to claim 9, characterized in that: The reference electrode (4) comprises a bottom electrode (41) and a chlorination layer (42) arranged on a surface of the bottom electrode (41) facing away from the flexible substrate (1).

11. The method for manufacturing a microelectrode structure according to claim 8, characterized in that: The reference electrode (4) is disposed on both the upper and lower surfaces of the flexible substrate (1), and the reference electrode (4) comprises a bottom electrode (41) and a chlorination layer (42) disposed on the surface of the bottom electrode (41) facing away from the flexible substrate (1). The manufacturing of corresponding electrode units on the upper surface and the lower surface of the flexible substrate (1) specifically includes: A rigid substrate (9) is provided, a temporary bonding layer (10) is made on the rigid substrate (9), and the flexible substrate (1) is attached to the temporary bonding layer (10). A bottom electrode (41) of one of the reference electrodes (4) and other electrode units on the same surface of the reference electrode (4) are manufactured on the surface of the flexible substrate (1) facing away from the rigid substrate (9); The flexible substrate (1), the temporary bonding layer (10) and the rigid substrate (9) are separated, and a temporary bonding layer (10) is formed on the rigid substrate (9), the flexible substrate (1) and the electrode unit thereon are turned over, and the side of the flexible substrate (1) provided with the electrode unit is attached to the temporary bonding layer (10) on the rigid substrate (9), A bottom electrode (41) of another reference electrode (4) and other electrode units on the same surface of the reference electrode (4) are manufactured on the surface of the flexible substrate (1) facing away from the rigid substrate (9); The flexible substrate (1) and the electrode unit, the temporary bonding layer (10) and the rigid substrate (9) on the flexible substrate (1) are separated; The chlorination layer (42) is formed on the surfaces of the two bottom electrodes (41) facing away from the rigid substrate (9).

12. The method for manufacturing a microelectrode structure according to claim 10 or 11, characterized in that: The chlorinated layer (42) is formed by depositing silver on the surface of the bottom electrode (41) facing away from the flexible substrate (1) and converting part of the silver into silver chloride.

13. The method for manufacturing a microelectrode structure according to claim 8, characterized in that: The production method further comprises: Electrical connection parts (5) corresponding one-to-one to the electrode units and leads (6) connecting the electrical connection parts (5) and the electrode units in a one-to-one correspondence are made on the surface of the flexible substrate (1).

14. The method for manufacturing a microelectrode structure according to claim 8, characterized in that: The production method further comprises: After the corresponding electrode units are manufactured on the upper surface and the lower surface of the flexible substrate (1), A biosensitive material layer (7) is formed on the surface of the working electrode (3) facing away from the flexible substrate (1), A first biofunctional layer (81) is fabricated on the upper surface of the flexible substrate (1), and the first biofunctional layer (81) covers the electrode unit and the biosensitive substance layer (7) on the upper surface of the flexible substrate (1); and a second biofunctional layer (82) is fabricated on the lower surface of the flexible substrate (1), and the second biofunctional layer (82) covers the electrode unit and the biosensitive substance layer (7) on the lower surface of the flexible substrate (1).

15. The method for manufacturing a microelectrode structure according to claim 14, characterized in that: When the electrode units on the upper surface of the flexible substrate (1) constitute a first microelectrode system (11) and the electrode units on the lower surface of the flexible substrate (1) constitute a second microelectrode system (22), the biosensitive substance components contained in the biosensitive substance layer (7) on the surface of the working electrode (3) of the first microelectrode system (11) and the second microelectrode system (22) are the same or different.

16. The method for manufacturing a microelectrode structure according to claim 9 or 11, characterized in that: The material of the temporary bonding layer (10) is selected from organic silicone or acrylic materials, and the viscosity of the temporary bonding layer (10) is eliminated by irradiation with light or heating.

17. A sensor, characterized in that: A microelectrode structure comprising the microelectrode structure described in any one of claims 1 to 7 or a microelectrode structure manufactured by the method for manufacturing the microelectrode structure described in any one of claims 8 to 16.

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