CN112834584A

CN112834584A - Physiological parameter monitoring electrode and preparation method thereof

Info

Publication number: CN112834584A
Application number: CN201911168928.XA
Authority: CN
Inventors: 王蕾; 张永成; 韩明松
Original assignee: Shenzhen Guiji Sensing Technology Co ltd
Current assignee: Shenzhen Guiji Sensing Technology Co ltd
Priority date: 2019-11-25
Filing date: 2019-11-25
Publication date: 2021-05-25

Abstract

A first aspect of the present disclosure describes a monitoring electrode for a physiological parameter, comprising: the liquid crystal display device comprises a substrate layer, a first electrode layer, a first insulating layer, a second electrode layer, a second insulating layer, a third electrode layer and a third insulating layer, wherein a third window exposing the first electrode layer is formed on the back surface of the substrate layer. In the first aspect of the present disclosure, a vertically stacked three-electrode structure is employed, and the first electrode layer and the second electrode layer are exposed from the front surface direction and the back surface direction of the base layer, respectively, whereby the degree of freedom in design of the third window area can be increased, improving the sensitivity of the monitoring electrode. In addition, the monitoring electrode can be conveniently implanted by a user by optimizing the area of the sensing part. Further, the second aspect of the present disclosure describes a method for manufacturing a physiological parameter monitoring electrode, which enables manufacturing a physiological parameter monitoring electrode having an optimized sensing portion area, which is easily implanted and has improved sensitivity.

Description

Physiological parameter monitoring electrode and preparation method thereof

Technical Field

The present disclosure relates generally to a monitoring electrode for physiological parameters and a method of making the same.

Background

The electrochemical biosensor is characterized in that a sensitive substance responding to an analyte is fixed on the surface of an electrode, then target molecules are captured on the surface of the electrode through the specific recognition effect among biological molecules, a concentration signal can be converted into measurable electric signals such as potential, current, resistance or capacitance through a working electrode, and the measured electric signals and the analyte concentration are in a linear relation under a certain condition, so that the quantitative or qualitative analysis of the target analyte is realized. Electrochemical biosensors, such as implantable electrochemical biosensors, typically require the use of biocompatible materials in order to continuously measure changes in a physiological parameter of an organism, such as glucose, over a period of time (e.g., 7 days) after implantation in the body. Taking a continuous blood glucose monitoring sensor as an example, the continuous blood glucose monitoring sensor uses glucose oxidases as sensitive substances responding to analytes, and can continuously monitor the blood glucose change condition in a human body in real time, thereby helping a patient to manage blood glucose.

For electrochemical biosensors, the requirements on the manufacturing process are relatively high, since integrated microstructures, microsensors, microactuators, etc. are usually required. Currently, electrochemical biosensors such as continuous blood glucose monitoring sensors are manufactured using, for example, Micro-Electro-Mechanical systems (MEMS). Compared with the screen printing technology, the MEMS utilizes the photoetching technology, the etching technology, the film technology and the like, and has the advantages of high manufacturing precision, high repeatability, mature process and easiness in batch production.

However, the existing technology of using the MEMS technology to fabricate the implantable electrochemical biosensor mostly uses a planar structure design, that is, the working electrode, the counter electrode and the reference electrode as the sensing part are arranged in the same plane, which results in a larger size of the fabricated sensor, which is not favorable for the user to conveniently implant, and affects the use experience. Furthermore, in order to make the area of the working electrode sufficient for adding a sufficient amount of sensitive substance responsive to the analyte, the area of the counter electrode is compressed and the speed of ion movement is correspondingly slowed down, resulting in a decrease in the sensitivity of the sensor.

Disclosure of Invention

The present disclosure has been made in view of the above-mentioned state of the art, and an object thereof is to provide a monitoring electrode of a physiological parameter capable of optimizing the area of a sensing part, being easily implanted, and improving sensitivity, and a method of manufacturing the same.

To this end, a first aspect of the present disclosure provides a monitoring electrode of a physiological parameter, comprising: a base layer having a front side and a back side opposite the front side; a first electrode layer disposed on the front side of the substrate layer having a first predetermined pattern; a first insulating layer disposed on the first electrode layer and having a first channel exposing the first electrode layer; a second electrode layer disposed on the first insulating layer, having a second predetermined pattern; a second insulating layer disposed on the second electrode layer and having a first window and a second channel exposing the second electrode layer; a third electrode layer disposed on the second insulating layer and having a third predetermined pattern; and a third insulating layer disposed on the third electrode layer and having a second window and a third channel exposing the third electrode layer, wherein a third window exposing the first electrode layer is formed on a rear surface of the substrate layer.

In the first aspect of the present disclosure, a stacked three-electrode structure is employed, and the first window exposes the surface of the second electrode layer from the front direction of the base layer, and the third window exposes the surface of the first electrode layer from the back direction of the base layer, in which case the size of the area of the third window can be free from the limitation of the sizes of the areas of the first window and the second window, so that the degree of freedom in designing the area of the third window can be increased, and the sensitivity of the monitoring electrode can be improved. Moreover, by optimizing the area of the sensing part, the user can conveniently implant the monitoring electrode.

In the physiological parameter monitoring electrode according to the first aspect of the present disclosure, the first channel may penetrate through the surface of the third insulating layer to expose the first electrode layer, the second channel may penetrate through the surface of the third insulating layer to expose the second electrode layer, and the first window may penetrate through the surface of the third insulating layer to expose the second electrode layer. Thereby, the respective electrode layers can be exposed on the same side of the third insulating layer.

In addition, in the monitoring electrode for physiological parameters according to the first aspect of the present disclosure, the area of the third window is optionally not smaller than the area of the first window. In this case, it can be ensured that the area of the first electrode layer exposed by the third window is not smaller than the area of the second electrode layer exposed by the first window.

In addition, in the monitoring electrode for physiological parameters according to the first aspect of the present disclosure, the monitoring electrode may have a detection end and a connection end, and the first window, the second window, and the third window may be formed in the detection end. Thereby, the first window, the second window, and the third window can be conveniently disposed at one end.

In the monitoring electrode for physiological parameters according to the first aspect of the present disclosure, the first electrode layer, the second electrode layer, and the third electrode layer may not be connected to each other. In this way, the first electrode layer, the second electrode layer, and the third electrode layer can have independent electrode functions.

In addition, in the monitoring electrode for physiological parameters according to the first aspect of the present disclosure, a sensitive substance responsive to an analyte is optionally disposed on an electrode surface of the second electrode layer located in the first window. In this case, a sensitive substance responding to the analyte specifically reacts with a target analyte (e.g., blood glucose, etc.) in the body, and the concentration of the target analyte can be sensed by the reaction.

Further, in the monitoring electrode for physiological parameters according to the first aspect of the present disclosure, the detection end is optionally disposed with a biocompatible coating. Thus, the portion implanted in the body can have high biocompatibility.

In addition, in the monitoring electrode for physiological parameters according to the first aspect of the present disclosure, the connecting end is optionally in a tridentate structure, and the first channel, the second channel, and the third channel are respectively located on three branches of the tridentate structure. From this, can conveniently operate monitoring electrode through the special fixture with trident shape structure complex.

In addition, in the monitoring electrode for physiological parameters according to the first aspect of the present disclosure, the connection end is optionally elongated, and the first channel, the second channel, and the third channel are arranged along a length direction of the connection end. Thus, the monitoring electrode can be operated easily.

In the monitoring electrode for physiological parameters according to the first aspect of the present disclosure, a welding layer may be formed in the first channel. Therefore, the first electrode layer can be conveniently conducted through a welding mode.

In addition, a second aspect of the present disclosure provides a method for preparing a monitoring electrode for physiological parameters, comprising the steps of: (a) preparing a substrate having a front surface and a back surface, and forming a base layer on the front surface of the substrate; (b) forming a first electrode layer having a first predetermined pattern on the base layer, and then forming a first insulating layer; (c) forming a second electrode layer having a second predetermined pattern on the first insulating layer, and then forming a second insulating layer; (d) forming a third electrode layer having a third predetermined pattern on the second insulating layer, and then forming a third insulating layer; (e) forming a patterned mask layer on the third insulating layer and etching the patterned mask layer to form a first window on the second electrode layer and a second window on the third electrode layer; and (f) patterning and etching the back surface of the substrate to form a third window in the base layer.

In the second aspect of the present disclosure, a stacked three-electrode structure is employed, and the first window exposing the second electrode layer exposes the surface of the second electrode layer from the front surface direction of the base layer, and the third window exposes the surface of the first electrode layer from the back surface direction of the base layer, in which case the size of the area of the third window can be free from the limitation of the sizes of the areas of the first window and the second window, so that the degree of freedom in designing the area of the third window can be increased, and the sensitivity of the monitor electrode can be improved. Moreover, by optimizing the area of the sensing part, the user can conveniently implant the monitoring electrode.

In addition, in the manufacturing method according to the second aspect of the present disclosure, optionally, in the step (a), a first sacrificial layer is formed between the front surface of the substrate and the base layer, and the first sacrificial layer is patterned. Thereby, formation of the base layer in a predetermined pattern on the patterned first sacrificial layer can be facilitated.

In addition, in the production method relating to the second aspect of the present disclosure, optionally, before step (c), the first insulating layer is further patterned and a through hole communicating with the first electrode layer is formed, and in step (c), a soldering layer connected to the first electrode layer is further formed in the through hole. In this case, the first electrode layer can be easily connected to the second electrode layer through the solder layer by soldering.

In addition, in the production method relating to the second aspect of the present disclosure, optionally, in step (e), a first channel is further formed on the first electrode layer, a second channel is formed on the second electrode layer, and a third channel is formed on the third electrode layer. Thereby, the respective electrode layers can be exposed on the same side of the third insulating layer.

In addition, in the manufacturing method according to the second aspect of the present disclosure, optionally, in the step (f), after the third window is formed, the first sacrificial layer and the substrate are removed by etching the first sacrificial layer. Thereby, the monitor electrode can be obtained by removing the first sacrificial layer and the substrate with ease.

In the production method according to the second aspect of the present disclosure, optionally, in the step (b), the first electrode layer is formed by forming a patterned second sacrificial layer on the base layer, forming a metal layer, and then peeling off the second sacrificial layer. Thereby, the first electrode layer having the first predetermined pattern can be formed on the base layer by the lift-off process.

In addition, in the production method according to the second aspect of the present disclosure, a low resistance layer may be optionally formed on an electrode surface of the second electrode layer located in the first window. Thereby, the impedance of the surface of the second electrode layer exposed by the first window can be reduced.

In addition, in the production method relating to the second aspect of the present disclosure, optionally, the low resistance layer is formed by plating one of platinum ash, platinum black, or a combination thereof on the surface of the electrode. This facilitates formation of a low resistance layer having a granular feel.

In addition, in the production method according to the second aspect of the present disclosure, a composite dielectric film including a silicon dioxide layer and a silicon nitride layer stacked in this order may be formed on each of the front surface and the back surface of the substrate. In this case, the composite dielectric film can act as a barrier to etching.

In addition, in the manufacturing method according to the second aspect of the present disclosure, optionally, in step (f), the silicon nitride layer on the back surface of the substrate is patterned and etched, and is etched to the surface of the first electrode layer, so as to form the third window. Thereby enabling the third window to be conveniently formed on the rear surface of the substrate.

According to the present invention, the monitoring electrode for physiological parameters has a stacked three-electrode structure, and the first window exposing the second electrode layer exposes the surface of the second electrode layer from the front side of the base layer, and the third window exposes the surface of the first electrode layer from the back side of the base layer. Moreover, by optimizing the area of the sensing part, the user can conveniently implant the monitoring electrode.

Drawings

Fig. 1 is a schematic diagram illustrating a use state of a glucose monitoring probe according to an embodiment of the present disclosure.

Fig. 2 is a schematic perspective view of a biocompatible coating of a monitoring electrode for physiological parameters according to an embodiment of the present disclosure.

Fig. 3a is a plan view showing one configuration of a physiological parameter monitoring electrode according to an embodiment of the present disclosure, and fig. 3b is a bottom view showing one configuration of a physiological parameter monitoring electrode according to an embodiment of the present disclosure.

Fig. 4 is a top view of another configuration of a monitoring electrode for physiological parameters according to an embodiment of the present disclosure.

Fig. 5 is a schematic perspective view of a monitoring electrode showing the physiological parameters referred to in fig. 3a and 3 b.

Fig. 6 is a view along line L-L' in fig. 5.

Fig. 7 is a flow chart illustrating a method of making a physiological parameter monitoring electrode according to an embodiment of the present disclosure.

Fig. 8a to 8d are schematic perspective views illustrating an exploded step of step (b) in a method for manufacturing a physiological parameter monitoring electrode according to an embodiment of the present disclosure.

Fig. 9a to 9c are schematic plan views illustrating a decomposition step of step (e) in the manufacturing method according to the embodiment of the present disclosure.

Fig. 10a to 10d are schematic plan views illustrating an exploded step of step (f) in a manufacturing method according to an embodiment of the present disclosure.

Detailed Description

Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. In the following description, the same components are denoted by the same reference numerals, and redundant description thereof is omitted. The drawings are schematic and the ratio of the dimensions of the components and the shapes of the components may be different from the actual ones.

In the present disclosure, the monitoring electrode for physiological parameters may be simply referred to as "monitoring electrode", and the preparation method of the monitoring electrode for physiological parameters may be simply referred to as "preparation method". The monitoring electrode for physiological parameters according to the present disclosure can be used, for example, in a blood glucose monitoring device for monitoring blood glucose, a uric acid monitoring device for monitoring uric acid, a cholesterol monitoring device for detecting cholesterol, and the like.

Fig. 1 is a schematic diagram illustrating a use state of a glucose monitoring probe according to an embodiment of the present disclosure. Fig. 2 is a perspective view of a biocompatible coating 111 of a monitoring electrode 1 showing physiological parameters according to an embodiment of the present disclosure. Fig. 3a is a top view of one example of the monitoring electrode 1 showing a physiological parameter according to an embodiment of the present disclosure. Fig. 3b is a bottom view of one example of the monitoring electrode 1 showing a physiological parameter according to the embodiment of the present disclosure.

In the present embodiment, in some examples, the monitoring electrode 1 may include a detection terminal 11 and a connection terminal 12. The detection tip 11 has a sensing portion for detecting a physiological parameter, and when the physiological parameter is continuously monitored using the monitoring electrode 1 for physiological parameter according to the present embodiment, the detection tip 11 may be implanted into a living body (for example, a superficial skin layer or the like), the sensing portion may specifically react with a target analyte in the living body, and chemical information during the reaction may be converted into a signal that can be measured, for example, an electrical signal, by the monitoring electrode 1 under a certain condition. In some examples, the connection end 12 may be connected to an electronic system 6 including a signal processing system for processing and analyzing, for example, an electric signal and a display for displaying monitoring data, and the electric signal measured by the monitoring electrode 1 is analyzed in real time and displayed on the display, thereby performing real-time continuous monitoring of a parameter of a target analyte in a living organism. Thereby enabling the physiological parameter of the target analyte to be obtained. In some examples, the monitoring device of the physiological parameter may include the monitoring electrode 1 and the electronic system 6, as described above.

In the present embodiment, in some examples, the monitoring electrode 1 of the physiological parameter may include: a base layer 21 having a front side and a back side opposite the front side; a first electrode layer 31 provided on the front side of the base layer 21, having a first predetermined pattern; a first insulating layer 22 disposed on the first electrode layer 31 and having a first channel 221 exposing the first electrode layer 31; a second electrode layer 32 disposed on the first insulating layer 22 and having a second predetermined pattern; a second insulating layer 23 disposed on the second electrode layer 32 and having a first window 231 and a second channel 232 exposing the second electrode layer 32; in which, on the back surface of the substrate layer 21, there is also a third window 211 exposing the first electrode layer 31.

In other examples, the monitoring electrode 1 for physiological parameters may further include a third electrode layer 33 disposed on the second insulating layer 23 and having a third predetermined pattern; and a third insulating layer 24 disposed on the third electrode layer 33 and having a second window 241 and a third channel 242 exposing the third electrode layer 33. In this case, the monitoring electrode 1 has a three-electrode structure, and the third electrode layer 33 is added compared with a two-electrode structure, so that the voltage generated by the second electrode layer 32 can be more accurately obtained, and thus, the accuracy of physiological parameter measurement can be improved.

In the present embodiment, an analyte-responsive sensitive substance 322 (described later) that specifically reacts with a target analyte may be disposed on the surface of the third electrode layer 33 exposed by the second window 241. In addition, the detection tip 11 may be coated with a biocompatible coating 111 (described later).

In the first aspect of the present disclosure, a stacked three-electrode structure is employed, and the first window 231 exposes the surface of the second electrode layer 32 from the front surface direction of the base layer 21, and the third window 211 exposes the surface of the first electrode layer 31 from the back surface direction of the base layer 21, in which case the area size of the third window 211 can be free from the limitation of the area sizes of the first window 231 and the second window 241, so that the degree of freedom in designing the area of the third window 211 can be increased, and the sensitivity of the monitor electrode 1 can be improved. Moreover, by optimizing the area of the sensing portion, it is possible to facilitate the user to implant the monitoring electrode 1.

The physiological parameter monitoring electrode is not limited to the glucose monitoring electrode, and the physiological parameter monitoring electrode according to the present embodiment may be, for example, a uric acid monitoring electrode obtained by replacing glucose oxidase with uricase, a cholesterol monitoring electrode obtained by replacing glucose oxidase with cholesterol oxidase, or the like by replacing the analyte-responsive sensing substance 322 in the sensing portion of the monitoring electrode 1. For those skilled in the art, the glucose monitoring electrode described later can be applied to the monitoring electrode for other physiological parameters such as uric acid monitoring electrode and cholesterol monitoring electrode with ordinary modifications without creative work.

In the present disclosure, a portion of the second electrode layer 32 exposed by the first window 231 may also be simply referred to as a second electrode, a portion of the third electrode layer 33 exposed by the second window 241 may be simply referred to as a third electrode, and a portion of the first electrode layer 31 exposed by the third window 211 may be simply referred to as a first electrode. In the monitoring electrode (glucose monitoring electrode) 1, in some examples, the first electrode is sometimes also referred to as a counter electrode, the second electrode is sometimes also referred to as a working electrode, and the third electrode is sometimes also referred to as a reference electrode.

In the present embodiment, the monitoring electrode 1 may include a detection tip 11. In some examples, the sensing end 11 may be elongated. In this case, the first window 231 and the second window 241 may be compactly disposed on one surface of the detection terminal 11, and the third window 211 may be oppositely disposed on the other surface of the detection terminal 11, so that the first window 231, the second window 241 and the third window 211 expose the corresponding electrode layer surfaces on the opposite surfaces of the detection terminal 11, thereby reducing the area of the detection terminal 11, that is, the depth of the monitoring electrode 1 implanted into the body, and thus reducing the discomfort caused by the implantation.

Generally, when the detecting end 11 has an elongated shape (see fig. 3a and 3b), the detecting end 11 can be easily implanted into the body. The monitoring electrode 1 is implanted in a living body in a different manner depending on the hardness of the material used for the monitoring electrode. When the hardness of the material used for the monitoring electrode 1 is large enough, the detection end 11 is long, so that the detection end can conveniently and directly penetrate into the body. When the monitoring electrode 1 is made of a material having insufficient hardness, or in order to prevent the monitoring electrode 1 from being damaged, it may be implanted into the body with the aid of an implantation-assisting instrument such as a needle assist device or a notched puncture needle. The needle booster is internally provided with a long strip-shaped needle head with a U-shaped groove, and when the detection end 11 is long strip-shaped, the long strip-shaped needle head can be matched with the needle head of the needle booster and implanted into a body with the help of the needle booster. However, the present disclosure is not limited thereto, and in other cases, the detection end 11 may have a flat and wide rectangle shape, a circular disc shape, an elliptical disc shape, a spoon shape, or an irregular shape.

In this embodiment, the detection tip 11 may be coated with a biocompatible coating 111. In some examples, the biocompatible coating 111 may be a semi-permeable membrane having biocompatibility. In this case, since the semipermeable membrane has a diffusion control effect, it is possible to effectively prevent the non-target analyte in the body from contacting the analyte-responsive sensitive substance 322 of the monitoring electrode 1, thereby achieving an anti-interference effect. In addition, in some examples, the biocompatible coating 111 can have a diffusion control effect, and thus can control the rate of diffusion of the target analyte to the second electrode and the number of molecules, i.e., control the ratio of the number of target analyte to analyte-responsive susceptible substance 322 such that the number of analyte-responsive susceptible substance 322 is always greater than the number of target analyte, ensuring the sufficiency of the reaction when the change in the electrical signal generated by the monitoring electrode 1 is substantially affected only by the change in the concentration of the target analyte in the body fluid. This can improve the accuracy of measurement by the monitor electrode 1. In some examples, when the analyte is glucose in blood or tissue fluid, the interferent commonly used in the measurement may include uric acid, ascorbic acid, acetaminophen, etc. commonly existing in the body, in which case, the biocompatible coating 111 with corresponding function is selected to block the interferent outside the semipermeable membrane, and the substance penetrating through the semipermeable membrane is mainly the target analyte, thereby improving the measurement accuracy of the monitoring electrode 1. In some examples, when the analyte is glucose in blood, a suitable semi-permeable membrane may be selected as the biocompatible coating 111 such that the glucose concentration reaching the second electrode is reduced by a factor of 10 to 100, preferably 30 to 80, compared to the glucose concentration in blood. In this case, the amount of glucose diffusing to the second electrode can be reduced, and a sufficient amount of the sensitive substance 322 responding to the analyte, such as glucose oxidase or dehydrogenase, and other substances participating in the reaction can be ensured, so that the glucose concentration becomes a factor that mainly limits the change of the electric signal of the monitoring electrode 1, such as the change of the current magnitude, and thus the change of the electric signal of the monitoring electrode 1 can correctly reflect the change of the glucose concentration in the body fluid, and the linear range of the monitoring probe 1 can be increased to a large extent, thereby improving the measurement accuracy of the monitoring electrode 1.

In some examples, the biocompatible coating 111 may be made of a plant material. The plant material can be at least one of sodium alginate, tragacanth gum, pectin, acacia, xanthan gum, guar gum, agar, etc., and natural material derivatives. The natural material derivative may include a starch derivative or a cellulose derivative, among others.

In this embodiment, the biocompatible coating 111 may cover only the detection end 11 of the monitoring electrode 1. This can reduce the use of raw materials. Examples of the present disclosure are not limited thereto, and in some examples, the biocompatible coating 111 may cover the entire monitoring electrode 1. Therefore, the monitoring electrode 1 can be ensured to have biocompatibility when implanted into different depths in the body.

In the present embodiment, as described above, the monitoring electrode 1 may further include the connection terminal 12. The connection terminal 12 is provided with a first channel 221 exposing a surface of the first electrode layer 31, a second channel 232 exposing a surface of the second electrode layer 32, and a third channel 242 exposing a surface of the third electrode layer 33 (see fig. 3 and 5), whereby the monitoring electrode 1 can be accessed to a supporting electronic system 6 including a signal processing system and a display through the exposed surface of the electrode layer.

In some examples, the shape of the first channel 221, the second channel 232, and the third channel 242 may each be one of rectangular, circular, elliptical, triangular, trapezoidal, or irregular.

In the present embodiment, in some examples, the connection end 12 may have an elongated shape, and in this case, the first channel 221, the second channel 232, and the third channel 242 may be aligned along the length direction of the connection end 12. In some examples, the first, second, and

third channels

221, 232, 242 may be equally spaced on the same axis on the connection end 12. In other examples, the first, second and

third passages

221, 232, 242 may also be off-axis at the connection end 12 and spaced at different distances from each other.

In some examples, as shown in fig. 4, the connection end 12 may have a trident structure (see fig. 4), in which case the first, second and

third channels

221, 232, 242 are located on three branches of the trident structure, respectively, and the first, second and

third channels

221, 232, 242 may be sequentially arranged. However, the present embodiment is not limited thereto, and the first channel 221, the second channel 232, and the third channel 242 may be located on any branch, and there is no fixed order among the three channels. For example, the first channel 221 may be disposed in the middle branch or disposed in the two branches.

In other examples, the connection end 12 may be Y-shaped. In this case, for example, the first channel 221 and the second channel 232 may be located in one branch of the wye while the third channel 242 is located in the other branch of the wye.

In some examples, the shape of the third window 211, the first window 231, and the second window 241 may be one of a rectangle, a circle, an ellipse, a triangle, a trapezoid, or an irregular shape, respectively.

In addition, in the present embodiment, the monitoring electrode 1 may be implanted in the body for 1 day to 1 month or even longer depending on the actual target analyte, condition of the organism, and the like. For example, it may be implanted in a human body for 1 to 24 days, preferably 7 to 14 days. In addition, as described above, the biocompatible coating 111 having the function of the semipermeable membrane can restrict the entry of a part of the target analyte and the electroactive interfering substance other than the non-target analyte, effectively extend the linear range of the monitoring electrode 1, and stabilize the life cycle of the monitoring electrode 1 by allowing the target analyte to react with the sensing substance 322 responding to the analyte better.

Fig. 5 is a schematic perspective view of a monitoring electrode for physiological parameters according to an embodiment of the present disclosure. Fig. 6 is a schematic view showing a cross section along L-L' in fig. 5.

In the present embodiment, as described above, the monitoring electrode 1 may include the base layer 21 (see fig. 6). In some examples, the base layer 21 may be in the shape of a long strip. Additionally, in some examples, the shape of the base layer 21 may also be trident, binary, irregular, etc.

In this embodiment mode, the materials of the base layer 21, the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 may be selected from flexible insulating materials. In some examples, the flexible insulating material may be at least one of Polyimide (PI), polyethylene terephthalate (PET), poly-xylylene (Parylene), silicone, Polydimethylsiloxane (PDMS), polyethylene glycol (PEG), or polytetrafluoroethylene (Teflon), Polyethylene (PE), polypropylene (PP), Polystyrene (PS), polyethylene naphthalate (PEN), and the like. In this case, the base layer 21, the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 may be made of a flexible insulating material, and thus both flexibility and insulation can be achieved, and discomfort after implantation in a body can be reduced.

In some examples, the base layer 21, the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 may also be made of non-flexible materials. The non-flexible material may generally comprise ceramic, Polymethylmethacrylate (PMMA), alumina or silica, or the like. In this case, the monitoring electrode 1 may be made into a rigid structure such as a rigid needle tip, so that the monitoring electrode 1 can be implanted into the body surface (e.g., the superficial layer of the skin, etc.) without an auxiliary implantation device (not shown).

In other examples, in the monitor electrode 1, the portions of the base layer 21, the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 located at the detection end 11 may be made of a flexible material, and the portions of the base layer 21, the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 located at the connection end 12 may be made of a non-flexible material.

In the present embodiment, the thickness of the base layer 21 may be 100-200 μm, for example, the base layer, in which case the base layer 21 may have good supporting performance.

In the present embodiment, the substrate layer 21 may include a third window 211, and the third window 211 may expose a surface of the first electrode layer 31. In addition, the third window 211 may be disposed at a side of the base layer 21 at the sensing end 11, and thus, the first electrode may be correspondingly disposed at a side of the sensing end 11. In addition, when the detection tip 11 is implanted in the body, the first electrode of the first electrode layer 31 exposed by the third window 211 may be connected to the second electrode of the second electrode layer 32 by body fluid to form a passage.

In some examples, the third window 211 may penetrate through the substrate layer 21 in a width direction of the substrate layer 21, whereby an area of the first electrode layer 31 exposed by the third window may be increased as much as possible. In other examples, third window 211 may not extend through substrate layer 21. In this case, the first electrode layer 31 can be protected, and the durability of the monitor electrode 1 can be improved.

In some examples, the third window 211 may vertically expose the first electrode from the back surface of the base layer 21, in other words, a sidewall of the third window 211 is perpendicular to a surface of the first electrode. However, the examples of the disclosure are not limited thereto, in other examples, the third window 211 may gradually expose the first electrode from the back surface of the substrate layer 21, in other words, the window area of the third window 211 on the surface of the back surface of the substrate layer 21 is larger than the window area exposing the first electrode, and the connection between the two is a smooth slope, a step slope, an irregular slope, or a curved surface, an irregular curved surface, etc.

In this embodiment, since the third window 211 is provided on one side (for example, the back surface) of the base layer 21 and the first window 231 and the second window 241 are provided on the other side (for example, the front surface) of the base layer 21, the size of the area of the third window 211 can be free from the size of the areas of the first window 231 and the second window 241, and thus the degree of freedom in designing the area of the third window 211 can be increased and the sensitivity of the monitor electrode 1 can be improved. Moreover, by optimizing the area of the sensing portion, the user can conveniently implant the monitoring electrode 1.

In the present embodiment, the area of the third window 211 may be not smaller than the area of the first window 231, in other words, the area of the first electrode is not smaller than the area of the second electrode, whereby the sensitivity of the monitoring electrode 1 can be further improved. As described above, when the monitoring electrode 1 is implanted in the body, the second electrode and the first electrode are communicated with each other by the body fluid therebetween, and when the area of the first electrode is not smaller than that of the second electrode, the ion moving speed between the two electrodes is faster, and therefore, the ions can move from the second electrode to the first electrode at a faster speed, so that the sensitivity of the monitoring electrode 1 can be improved.

In addition, in some examples, the area of the third window 211 may be not less than the sum of the area of the first window 231 and the area of the second window 241. This can further improve the sensitivity of the monitor electrode 1.

In the present embodiment, the monitoring electrode 1 may include a first electrode layer 31 (see fig. 6), and the first electrode layer 31 is disposed on the base layer 21 and closely attached to the base layer 21. The surface of the first electrode layer 31 exposed by the third window 211 is a first electrode, the surface exposed by the first channel 221 is a first pad, and a portion of the first electrode layer 31 connecting the first electrode and the first pad is a first connection line. The surface of the second electrode layer 32 exposed by the first window 231 is a second electrode, the surface exposed by the second via 232 is a second pad, and a portion of the second electrode layer 32 connecting the second electrode and the second pad is a second connection line. The surface of the third electrode layer 33 exposed by the second window 241 is a third electrode, the surface exposed by the third channel 242 is a third pad, and a portion of the third electrode layer 33 connecting the third electrode and the third pad is a third connection line.

In some examples, the width of the first electrode layer 31 is less than the width of the base layer 21 and the first insulating layer 22. In this case, the first electrode layer 31 may be completely covered by the base layer 21 and the first insulating layer 22, and the first connection portion of the first electrode layer 31 is not directly exposed to a liquid environment after being implanted in a body, whereby the durability of the monitoring electrode 1 and the accuracy of measurement can be improved.

In this embodiment, the first electrode layer 31, the second electrode layer 32, and the third electrode layer 33 have conductivity. In some examples, the first electrode layer 31, the second electrode layer 32, and the third electrode layer 33 may be made of at least one of silver, platinum, gold, titanium, palladium, iridium, niobium, or an alloy thereof, respectively. This enables the first electrode layer 31, the second electrode layer 32, and the third electrode layer 33 to have good conductivity. In other examples, the first electrode layer 31, the second electrode layer 32, and the third electrode layer 33 may also be made of a non-metal material having conductivity, such as glassy carbon, graphite, and the like, respectively.

In some examples, when the base layer 21 and the first insulating layer 22 are made of flexible polyimide, the first electrode layer 31 may be a Ti-Pt-Ti composite metal structure. This makes it possible to make the first electrode layer 31 have good electrical conductivity and less likely to fall off.

In the present embodiment, in some examples, the thicknesses of the first electrode layer 31, the second electrode layer 32, and the third electrode layer 33 may be respectively 100-. Thereby, the first electrode layer 31 may have good conductive properties.

As described above, when the monitoring electrode 1 is implanted in the body, the first electrode may communicate with the second electrode via the body fluid. Since the first electrode is exposed from the back surface of the base layer 21, the area of the first electrode can be increased as much as possible without being limited by the areas of the second electrode and the third electrode in the case where the area of the monitoring electrode 1 implanted in the body is constant.

In the present embodiment, the first electrode layer 31 may include a soldering layer 311. The soldering layer 311 is formed on a surface of the first electrode layer 31 exposed by the first via 221 (described later), whereby the first electrode layer 31 can be conveniently conducted by soldering.

In some examples, the soldering layer 311 may completely cover the surface of the first electrode layer 31 exposed by the first channel 221. For example, the area of the bonding layer 311 may be larger than that of the first pad, in which case, it is ensured that the first pad is entirely covered by the bonding layer 311, and thus the first electrode layer 31 can be easily conducted by a bonding method.

In the present embodiment, the monitoring electrode 1 may include a first insulating layer 22 (see fig. 6), and the first insulating layer 22 may be formed on the first electrode layer 31. In some examples, the first insulating layer 22 may cover the first electrode layer 31 such that the first connection line portion of the first electrode layer 31 is not exposed, and the first connection line portion does not directly contact with body fluid after the monitoring electrode 1 is implanted in a body, thereby increasing durability of the monitoring electrode 1 in use and stability and safety after implantation.

In the present embodiment, in some examples, the material categories of the base layer 21, the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 may be uniform. For example, flexible materials may be selected, or non-flexible materials may be selected, in which case, the overall support performance of the monitoring electrode 1 is relatively consistent, and the monitoring electrode is not easily broken or separated. In some examples, the base layer 21, the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 may all be made of the same material. In addition, in some examples, the base layer 21, the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 may be made of different materials of the same type.

In the present embodiment, in some examples, the thicknesses of the first, second, and third insulating

layers

22, 23, and 24 may be 1 to 10 μm, respectively, and in particular, the first insulating layer, in which case the first, second, and third insulating

layers

22, 23, and 24 can have good insulating properties, and thus, the electrode layers can be well separated.

In some examples, when the thickness of the first insulating layer 22 is greater than 100 μm and the thickness of the base layer 21 is 1 to 10 μm, in this case, the first insulating layer 22 of the monitor electrode 1 mainly plays a supporting role and the base layer 21 mainly plays an insulating role.

In the present embodiment, in some examples, the first insulating layer 22 may include a first channel 221, the first channel 221 may expose a surface (a first pad) of the first electrode layer 31, and the first channel 221 may be disposed at a side of the first insulating layer 22 at the connection terminal 12, thereby facilitating the monitor electrode 1 to connect the first electrode layer 31 to the electronic system 6 through the first channel 221 of the connection terminal 12.

In this embodiment, the first channel 221 may penetrate to the surface of the third insulating layer 24 to expose the first electrode layer 31. In other words, the first channel 221 can sufficiently expose the first pad of the first electrode layer 31, and when the first pad is not connected to the electronic system 6, the first pad is located at one end of the first channel 221, and the other end of the first channel 221 is not sealed, in particular, not sealed by the second electrode layer 32, the second insulating layer 23, the third electrode layer 33, and the third insulating layer 24 which are not located above the first pad.

In some examples, the first channel 221 may penetrate the first insulating layer 22 in a width direction of the first insulating layer 22. But examples of the present disclosure are not limited thereto, and in other examples, the first channel 221 may not penetrate the first insulating layer 22 in the width direction but leave a portion of the first insulating layer 22 in the width direction.

In this embodiment, the first channel 221 may vertically expose the first pad, in other words, a sidewall of the first channel 221 is perpendicular to a surface of the first pad. However, examples of the present disclosure are not limited thereto, and in other examples, the first channel 221 may not vertically expose the first pad, for example, the first channel 221 may gradually expose the first pad.

In the present embodiment, the monitoring electrode 1 may include a second electrode layer 32 (see fig. 6), and the second electrode layer 32 is disposed on the first insulating layer 22 and closely attached to the first insulating layer 22.

In some examples, the width of the second electrode layer 32 is less than the width of the first insulating layer 22 and the second insulating layer 32. In this case, the second electrode layer 32 may be completely covered by the first insulating layer 22 and the second insulating layer 32, and the second connection line portion of the second electrode layer 32 is not directly exposed to the liquid environment after being implanted in the body, thereby improving the durability of the monitoring electrode 1.

In some examples, the width of the second electrode layer 32 may be identical to the width of the first electrode layer 31. In addition, in other examples, the width of the second electrode layer 32 may not be the same as the width of the first electrode layer 31.

In some examples, the end of the second electrode layer 32 at the detection end 11 may be aligned with the end of the first electrode layer 31 at the detection end 11.

In some examples, as described above, the second electrode layer 32 may also be a composite metal layer, such as a Ti-Pt-Ti structure. In addition, the complex metal layer structure of the second electrode layer 32 may be different according to the material selected for the first insulating layer 22 or the second insulating layer 23.

In the present embodiment, as described above, the thickness of the second electrode layer 32 may be 1000nm, preferably 700nm and 100 nm. Thereby, the second electrode layer 32 may have good conductive performance.

In some examples, the second electrode exposed by the first window 231 has an area of a predetermined size. In general, the area of the first window 231 may be designed according to the size of the predetermined implantation area and the amount of the analyte-responsive sensitive substance 322 to be coated. Thus, it is possible to control the implantation area to be small while leaving an area sufficient to coat the sensitive substance 322 responsive to the analyte.

In this embodiment, the surface of the second electrode layer 32 exposed by the first window 231 may be provided with the low resistance layer 321. The material of the low resistance layer 321 may be a metal material formed with extremely fine particles, and for example, it may be platinum ash or platinum black or the like. In this case, the low resistance layer 321 may form a surface with slight roughness and granular feel on the surface of the second electrode layer 32, so that the surface area of the second window 241 can be increased, which is beneficial to increase the contact area of the analyte-responsive sensitive substance 322 and the second electrode, and promote the combination of the two, thereby reducing the resistance of the surface of the second electrode and improving the sensitivity of the monitoring electrode 1.

In some examples, the area of the low resistance layer 321 may be the same as the area of the second electrode. Examples of the present disclosure are not limited thereto, and in other examples, the area of low impedance layer 321 may be limited to only the area coated with sensitive substance 322 responsive to the analyte.

In this embodiment, the second electrode surface is further disposed with an analyte-responsive sensing substance 322, and the analyte-responsive sensing substance 322 can be selected according to the target analyte. In this case, the analyte-responsive sensing substance 322 may specifically react with the target analyte in the body, and an electrical signal may be generated at the surface of the second electrode during the reaction, so that the concentration of the target analyte may be detected according to the generated electrical signal.

In some examples, the analyte-responsive sensing substance 322 may be a mixed solution of an enzyme, a cationic polymer, and a redox electron mediator. For example, analyte-responsive sensing substance 322 can be a mixed solution of, for example, glucose oxidase or dehydrogenase, with a cationic polymer, a redox electron mediator such as ferricyanide, diazaphenanthrene, or ferrocene, and a crosslinking agent.

As the monitoring electrode 1 of the physiological parameter, in some examples, the analyte-responsive sensing substance 322 may be a specific reactant corresponding to acetylcholine, amylase, bilirubin, cholesterol, chorionic gonadotropin, creatine kinase, creatine, creatinine, DNA, fructosamine, glucose, glutamine, growth hormone, ketone body, lactate, oxygen, peroxide, prostate specific antigen, prothrombin, RNA, thyroid stimulating hormone, troponin, and the like.

In other examples, the analyte-responsive sensing substance 322 may not be limited to monitoring the physiological parameters, and the monitoring electrode 1 may monitor the concentration of the drug in the body fluid after changing the composition of the analyte-responsive sensing substance 322, for example, antibiotics (e.g., gentamicin, vancomycin, etc.), digitoxin, digoxin, theophylline, warfarin (warfarin), and the like.

In this embodiment, the monitoring electrode 1 may include a second insulating layer 23 (see fig. 6), and the second insulating layer 23 may be formed on the second electrode layer 32. In some examples, the second insulating layer 23 may cover the second electrode layer 32, so that the second wire portion of the second electrode layer 32 is not exposed, and the second wire portion of the second electrode layer 32 does not directly contact with body fluid after the monitoring electrode 1 is implanted in vivo, thereby increasing durability of the monitoring electrode 1 in use and stability after implantation.

In this embodiment mode, the thickness of the second insulating layer 23 may be 1 to 10 μm, and particularly, the second electrode layer 32 and the third electrode layer 33 can be well separated. In some examples, the thicknesses of the first, second, and third insulating

layers

22, 23, and 24 may be the same. However, the examples of the present disclosure are not limited thereto, and the thicknesses of the first insulating layer 22, the second insulating layer 23 and the third insulating layer 24 may also be different, for example, the thickness of the first insulating layer 22 is greater than the thickness of the second insulating layer 23 or the third insulating layer 24.

In this embodiment, the first window 231 may be opened on the second insulating layer 23 from the direction of the front surface of the base layer 21, and the third window 211 may be opened from the rear surface of the base layer 21, in other words, the direction in which the first window 231 exposes the second electrode and the direction in which the third window 211 exposes the first electrode are different. In this case, the second electrode may have a predetermined area capable of being coated with the sensing substance 322 sufficiently responsive to the analyte, and since the first electrode and the second electrode are not in the same layer or the same plane, the area of the first electrode can be not limited by the area of the second electrode, so that the degree of freedom in designing the area of the first electrode, that is, the area of the third window 211 can be increased, the area of the sensing portion can be optimized, and the sensitivity of the monitoring electrode 1 can be improved.

In this embodiment, the edge of the first window 231 near the detection end 11 and the edge of the third window 211 near the detection end 11 may be aligned, so that the implantation area of the monitoring electrode 1 can be reduced after the areas of the first electrode and the second electrode are determined, the area of the sensing portion is optimized, and the user can implant the monitoring electrode 1 conveniently. However, examples of the present disclosure are not limited thereto, and in some examples, an edge of the first window 231 near the detection end 11 and an edge of the third window 211 near the detection end 11 may not be aligned.

In this embodiment, the second insulating layer 23 may include a second channel 232, the second channel 232 may expose a surface (a second pad) of the second electrode layer 32, and the second channel 232 may be disposed on a side of the second insulating layer 23 at the connection terminal 12, thereby facilitating monitoring of the electrode 1 to connect the second electrode layer 32 to the electronic system 6 through the second channel 232 of the connection terminal 12.

In the present embodiment, the second channel 232 may penetrate to the surface of the third insulating layer 24 to expose the second electrode layer 32. In other words, the second via 232 can sufficiently expose the second pad of the second electrode layer 32, and when the second pad is not connected to the electronic system 6, the second pad is located at one end of the second via 232, and the other end of the second via 232 is not sealed, particularly, not sealed by the second insulating layer 23, the third electrode layer 33 and the third insulating layer 24 which are not located above the second via 232.

In this embodiment, the second via 232 may vertically expose the second pad, in other words, a sidewall of the second via 232 is perpendicular to a surface of the second pad. Examples of the present disclosure are not limited thereto, and in other examples, the second via 232 may not vertically expose the second pad, for example, the second via 232 may gradually shrink to expose the second pad.

In the present embodiment, the monitoring electrode 1 may include a third electrode layer 33 (see fig. 6), and the third electrode layer 33 is disposed on the second insulating layer 23 and closely attached to the second insulating layer 23. In some examples, the width of the third electrode layer 33 is smaller than the width of the second insulating layer 23 and the third insulating layer 24. In this case, the third electrode layer 33 may be completely covered by the second insulating layer 23 and the third insulating layer 24, and the third wiring portion of the third electrode layer 33 is not directly exposed to the liquid environment after being implanted in the body, thereby improving the durability of the monitoring electrode 1.

In some examples, the width of the third electrode layer 33 may be the same as the width of the first and second electrode layers 31 and 32. In addition, in other examples, the width of the third electrode layer 33 may not be the same as the widths of the first and second electrode layers 31 and 32, for example, the width of the third electrode layer 33 may be greater than or less than the widths of the first and second electrode layers 31 and 32.

In the present embodiment, referring to fig. 6, an end of the third electrode layer 33 close to the detection end 11 may not be aligned with an end of the second electrode layer 32 close to the detection end 11, for example, a projection of the end of the third electrode layer 33 close to the detection end 11 in a direction perpendicular to the substrate layer 21 has no overlapping portion with the second electrode. Thus, the third electrode and the second electrode can be exposed from the front surface of the base layer 21, and the third electrode does not block the second electrode. However, examples of the present disclosure are not limited thereto, and in some examples, an end of the third electrode layer 33 close to the detection end 11 may be aligned with an end of the second electrode layer 32 close to the detection end 11, for example, the second electrode and the third electrode are disposed in parallel in a width direction of the detection end 11, and thus, both the third electrode and the second electrode may still be exposed from a direction of the front surface of the base layer 21.

In this embodiment, the electrode portion of the third electrode layer 33 exposed by the second window 241 may be a third electrode (reference electrode) that may form a known and fixed potential difference with interstitial fluid or blood. In this case, the potential difference formed between the third electrode and the second electrode can be used as a reference value for measuring the potential difference between the second electrode and the body fluid, so that the measurement accuracy of the monitoring electrode 1 can be improved. Therefore, the electronic system 6 connected with the monitoring electrode 1 can automatically adjust and maintain the stability of the voltage at the second electrode according to the preset voltage value so as to ensure that the measured current signal can accurately reflect the concentration value of the analyte.

In the present embodiment, the third electrode layer 33 has conductivity as described above. In addition, as described above, the third electrode layer 33 may also have a composite metal layer structure. In this embodiment, the surface of the third electrode exposed by the second window 241 may be provided with a silver (Ag) plating layer, a silver chloride (AgCl) layer may be provided on the surface of the silver plating layer, and the Ag-AgCl layer may be formed on the composite metal layer, in which case the composite metal layer mainly serves as a connection line and a third pad. Thereby, a silver-silver chloride layer can be used as the third electrode.

In the present embodiment, the monitor electrode 1 may include a third insulating layer 24 (see fig. 6), and the third insulating layer 24 may be formed over the third electrode layer 33. In some examples, the third insulating layer 24 may cover the third electrode layer 33, thereby enabling to improve durability of use of the monitoring electrode 1 and safety after implantation.

In some examples, the second window 241 may vertically expose the third electrode (reference electrode) from the front direction of the base layer 21 on the third insulating layer 24, in other words, the sidewall of the second window 241 is perpendicular to the surface of the third electrode. However, examples of the present disclosure are not limited thereto, and in other examples, the second window 241 may expose the second electrode on the third insulating layer 24 in a direction shrinking from the front surface of the base layer 21.

In the present embodiment, the second window 241 may be opened on the third insulating layer 24 from the direction of the front surface of the base layer 21, the first window 231 may be opened on the second insulating layer 23 from the direction of the front surface of the base layer 21, and the third window 211 may be opened from the rear surface of the base layer 21, in other words, the direction in which the third electrode is exposed through the second window 241 and the direction in which the second electrode is exposed through the window 231 are the same, and are different from the direction in which the second electrode is exposed through the third window 211. In this case, since the second electrode and the third electrode are not in the same layer or the same plane as the first electrode, the area of the first electrode can be not limited by the areas of the second electrode and the third electrode. This increases the degree of freedom in designing the area of the first electrode, that is, the area of the third window 211, and improves the sensitivity of the monitor electrode 1. Moreover, by optimizing the area of the sensing portion, it is possible to facilitate the user to implant the monitoring electrode 1.

In this embodiment, the third insulating layer 24 may include a third via 242, the third via 242 may expose a surface (a third pad) of the third electrode layer 33, and the third via 242 may be disposed at a side of the third insulating layer 24 at the tab 12, thereby facilitating monitoring of the electrode 1 accessing the third electrode layer 33 to the electronic system 6 through the third via 242 of the tab 12.

In some examples, the third channel 242 and the first and

second channels

221, 232 may not communicate with each other. In this case, since the first insulating layer 22, the second insulating layer 23, and the third insulating layer 24 are made of insulating materials, the first electrode layer 31, the second electrode layer 32, and the third electrode layer 33 can be sufficiently isolated from each other, and independent electrode functions thereof can be ensured, so that the detection accuracy of the monitoring electrode 1 can be improved. In addition, in other examples, the first, second, and

third channels

221, 232, and 242 may communicate with each other without connecting the first, second, and third electrode layers 31, 32, and 33 to each other.

In some examples, the third via 242 may extend through the third insulating layer 24 in a width direction of the third insulating layer 24. In other examples, the third channel 242 may not penetrate the third insulating layer 24 in the width direction, but a part of the third insulating layer 24 may remain in the width direction, whereby the durability of the use of the monitoring electrode 1 can be improved.

Hereinafter, a method of manufacturing the monitoring electrode 1 will be described in detail with reference to the accompanying drawings.

Fig. 7 is a flowchart illustrating a method of manufacturing the monitoring electrode 1 for physiological parameters according to the embodiment of the present disclosure.

In the present embodiment, the manufacturing method of the monitor electrode 1 may include (see fig. 7) (a) preparing a substrate 41 having a front surface and a back surface, and forming a base layer 21 on the front surface of the substrate 41 (step S100); (b) forming a first electrode layer 31 having a first predetermined pattern on the base layer 21 and then forming a first insulating layer 22 (step S200); (c) forming a second electrode layer 32 having a second predetermined pattern on the first insulating layer 22, and then forming a second insulating layer 23 (step S300); (d) forming a third electrode layer 33 having a third predetermined pattern on the second insulating layer 23, and then forming a third insulating layer 24 (step S400); (e) forming a patterned mask layer 51 on the third insulating layer 24 and etching the patterned mask layer to form a first window 231 on the second electrode layer 32 and a second window 241 on the third electrode layer 33 (step S500); and (f) patterning and etching are performed on the back surface of the substrate 41, thereby forming a third window 211 on the base layer 21 (step S600).

In the method of manufacturing the monitor electrode 1 according to the present embodiment, in which the three-electrode structure is used in which the first window 231 exposing the second electrode layer 32 exposes the surface of the second electrode layer 32 from the front surface direction of the base layer 21 and the third window 211 exposes the surface of the first electrode layer 31 from the back surface direction of the base layer 21, the size of the area of the third window 211 can be set without being limited by the size of the areas of the first window 231 and the second window 241, and thus the degree of freedom in designing the area of the third window 211 can be increased and the sensitivity of the monitor electrode 1 can be improved. Moreover, by optimizing the area of the sensing portion, the user can conveniently implant the monitoring electrode 1.

As described above, in step S100, the substrate 41 having the front surface and the back surface is prepared, and the base layer 21 is formed on the front surface of the substrate 41. In this embodiment, the substrate 41 may be selected from one of glass, silicon dioxide, and silicon nitride. In the present embodiment, the base layer 21 is preferably made of a flexible material, and thus, the flexible monitoring electrode 1 can be manufactured, and the foreign body sensation can be reduced and the bending is less likely to occur at the time of implantation.

In some examples, on the front surface and the back surface of the substrate 41, a composite dielectric film 411 on the front surface of the substrate 41 and a composite dielectric film 412 on the back surface of the substrate 41 including a silicon oxide layer and a silicon nitride layer stacked in this order may be formed, respectively. Specifically, the composite dielectric film 411 and the composite dielectric film 412 can be formed by first oxidizing a 0-3 μm silicon dioxide layer on the front and back surfaces of the substrate 41, and then forming a 0-2 μm silicon nitride layer by plating, spin coating, evaporation, printing or extrusion. In this case, the composite dielectric film 411 and the composite dielectric film 412 can be used as barrier layers to prevent the monitoring electrode 1 from being damaged by excessive etching during subsequent etching, thereby improving the process precision.

In some examples, when forming the base layer 21 on the front side of the substrate 41, the first sacrificial layer 413 may be formed between the front side of the substrate 41 and the base layer 21 and the first sacrificial layer 413 may be patterned. Specifically, the material of the first sacrificial layer 413 may be selected from one of photoresist, aluminum, silicon oxide, chromium, and titanium. In addition, the patterning may be performed by a photolithography process, in which a mask having a predetermined pattern is first prepared, then a proper amount of photoresist is spin-coated on the surface of the first sacrificial layer 413, and the patterned first sacrificial layer 413 is obtained by exposure, development, etching, and photoresist removal. Examples of the disclosure are not limited thereto and in other examples, other patterning methods, such as surface modification or printing, may be used for patterning. Thus, formation of the base layer 21 on the patterned first sacrificial layer 413 in a predetermined pattern can be facilitated, while subsequent removal of the substrate 41 by removing the first sacrificial layer 413 can be facilitated.

In some examples, the base layer 21 with a thickness of 1-10 μm may be formed on the patterned first sacrificial layer 413 by plating, spin coating, evaporation, printing or extrusion, and then dried and cured in a vacuum environment in the presence of an inert gas such as nitrogen to obtain the base layer 21 with a predetermined pattern.

Fig. 8a to 8d are schematic perspective views illustrating an exploded step of step (b) in a process of manufacturing a monitoring electrode for physiological parameters according to an embodiment of the present disclosure, wherein fig. 8a is a schematic perspective view illustrating formation of a second sacrificial layer on a base layer; FIG. 8b is a schematic perspective view showing the patterning of the second sacrificial layer; FIG. 8c is a schematic perspective view showing the formation of a metal layer; fig. 8d is a perspective view illustrating peeling off the second sacrificial layer.

As described above, in step S200, the first electrode layer 31 having the first predetermined pattern is formed on the base layer 21, and then the first insulating layer 22 is formed. In the present embodiment, the first insulating layer 22 is preferably made of the flexible material. Thus, the flexible monitor electrode 1 can be easily produced, and the foreign substance sensation can be reduced and the electrode is not easily bent at the time of implantation.

In this embodiment, as shown in fig. 8a to 8d, the base layer 21 may be patterned first. Specifically, as shown in fig. 8a, a layer of photoresist, such as positive photoresist, negative photoresist, reverse photoresist or double-layer photoresist, may be spin-coated on the substrate layer 21; then, as shown in fig. 8b, the photoresist may be exposed and developed using a mask having a first predetermined pattern, and then the surface may be treated with plasma to form the first predetermined pattern on the photoresist; then, as shown in fig. 8c, a first electrode layer 31 of a metal layer may be formed on the surface of the photoresist having the first predetermined pattern using evaporation, sputtering, plating, or the like; finally, as shown in fig. 8d, the metal remaining on the surface and the photoresist is removed by a lift-off process, so as to obtain the first electrode layer 31 having the first predetermined pattern. In some examples, the first predetermined pattern may be in the shape of, for example, a bar, a trident, a wye, or the like. In other examples, the first predetermined pattern may match the overall profile of the monitoring electrode 1.

In some examples, when the first electrode layer 31 of the metal layer is formed on the surface of the photoresist having the first predetermined pattern, the titanium metal layer, the platinum metal layer, and the titanium metal layer may be formed by using evaporation, sputtering, plating, or the like, 3 times, and each layer may have a thickness of 10 to 500nm, respectively, whereby the first electrode layer 31 having a Ti-Pt-Ti composite metal layer structure can be formed.

In the present embodiment, the first insulating layer 22 may be formed on the first electrode layer 31 having the first predetermined pattern by plating, spin coating, evaporation, printing, or extrusion, and then dried and cured in a vacuum environment under an inert gas atmosphere, thereby obtaining the first insulating layer 22 capable of covering the first electrode layer 31.

As described above, in step S300, the second electrode layer 32 having the second predetermined pattern is formed on the first insulating layer 22, and then the second insulating layer 23 is formed. In this embodiment. The step of patterning and forming the metal layer in step S300 may adopt the step of step S200, and is not described herein again.

In some examples, before forming the second electrode layer 32, the first insulating layer 22 may be further patterned and a through hole communicating with the first electrode layer 31 may be formed, and in step S300, a soldering layer 311 connected to the first electrode layer 31 may be further formed in the through hole. During subsequent etching, the first channel 221 may expose the solder layer 311. In this case, the second electrode layer 32 can be formed simultaneously with the formation of the solder layer 311, and thus the first electrode layer 31 can be electrically connected to the solder layer 311.

As described above, in step S400, the third electrode layer 33 having the third predetermined pattern is formed on the second insulating layer 23, and then the third insulating layer 24 is formed. In this embodiment, the step of patterning and forming the metal layer in step S400 may adopt the step of step S200, and is not described herein again.

In some examples, patterning may be performed on the surface of the metal layer of the third electrode layer 33 and a predetermined pattern may be formed after the metal layer of the third electrode layer 33 is formed, and the patterning method may employ a photolithography technique; then, forming a metallic silver layer on the surface of the patterned third electrode layer 33 by evaporation, sputtering or plating; the monitoring electrode 1 formed with the metallic silver layer may then be placed on ferric chloride (FeCl)₃) Soaking in the solution for a certain time to form a silver chloride (AgCl) film on the surface of the metal silver layer. Thereby, the third electrode of Ag — AgCl can be formed on the surface of the third electrode layer 33 exposed by the second window 241.

Fig. 9a to 9c are schematic plan views illustrating an exploded step of step (e) in a process method according to an embodiment of the present disclosure, wherein fig. 9a is a schematic plan view illustrating a mask layer formed on a third insulating layer; FIG. 9b is a schematic plan view illustrating the patterning of the mask layer; fig. 9c is a schematic plan view showing etching according to the pattern formed after patterning.

As described above, in step S500, the patterned mask layer 51 is formed on the third insulating layer 24 and etched, so that the first window 231 is etched on the second electrode layer 32 and the second window 241 is etched on the third electrode layer 33.

In some examples, in step S500, when the patterned mask layer 51 is formed on the third insulating layer 24 and etched, the first channel 221 is also formed on the first electrode layer 31, the second channel 232 is formed on the second electrode layer 32, and the third channel 242 is formed on the third electrode layer 33. Thereby, the monitoring of the access of the electrode 1 to the electronic system 6 can be facilitated.

In this embodiment, as shown in fig. 9a, a mask layer 51 is first formed on the surface of the third insulating layer 24. The material of the mask layer 51 may be selected from one of photoresist, aluminum, silicon oxide, chromium, and titanium. For example, a hard aluminum layer of 0.1 to 3 μm may be formed as the mask layer 51 on the third insulating layer 24 after the plasma pretreatment by evaporation or sputtering.

In this embodiment, as shown in fig. 9b, the mask layer 51 is patterned. The patterning may be performed by a photolithography process, which includes first preparing a mask having a predetermined pattern, spin-coating a photoresist on the surface of the third insulating layer 24, exposing and developing to form a corrosion pattern, and etching in a corresponding etching solution to obtain the patterned mask layer 51. For example, when the material of the mask layer 51 is aluminum, the etching may be performed by using an aluminum etchant.

In some examples, a protective layer may be formed on the patterned masking layer 51, such as by coating with a photoresist. Therefore, the over-etching phenomenon can be prevented in the subsequent etching process. If the first electrode layer 31, the second electrode layer 32, and the third electrode layer 33 are of a Ti-Pt-Ti structure, the protective layer may not be formed, and the titanium layer on the surface may play a role in protection.

In this embodiment, as shown in fig. 9c, the patterned mask layer 51 is etched, such that the depth of the first window 231 just exposes the surface of the second electrode layer 32, the depth of the second window 241 just exposes the surface of the third electrode layer 33, the depth of the first channel 221 just exposes the surface of the first electrode layer 31, the depth of the pad layer 311 of the first electrode layer 31, the depth of the second channel 232 just exposes the surface of the second electrode layer 32, and the depth of the third channel 242 just exposes the surface of the third electrode layer 33. The etching method can be laser etching, plasma etching or chemical etching. In some examples, the etching may be accomplished by an Inductively Coupled Plasma (ICP) etcher, a Reactive Ion Etcher (RIE), or the like.

In some examples, after the etching is completed, the protective or masking layer 51, e.g., a dural layer, may be removed by a corresponding solution or etching liquid, e.g., an aluminum etching liquid.

Fig. 10a to 10c are schematic plan views illustrating an exploded step of step (f) in the process method according to the embodiment of the present disclosure, wherein fig. 10a is a schematic plan view illustrating patterning of a composite dielectric film on the back surface of a substrate; FIG. 10b is a schematic plan view showing etching of the substrate; FIG. 10c is a plan view illustrating etching of the base layer; FIG. 10d is a schematic plan view showing the removal of the first sacrificial layer and the substrate.

As described above, in step S600, patterning and etching are performed on the back surface of the substrate 41, thereby forming the third window 211 on the base layer 21. Specifically, in step S600, as shown in fig. 10a, the silicon nitride layer of the composite dielectric film 412 on the back surface of the substrate 41 may be patterned and etched, and this step may be optionally performed by using an ICP etcher; next, as shown in fig. 10b, the ICP etcher may be used again to etch until the base layer 21 is exposed; thereafter, as shown in fig. 10c, only the surface of the first electrode layer 31 may be etched using a RIE etcher, thereby forming the third window 211. In this case, since patterning and etching are performed on the back surface of the substrate 41, the third window 211 is formed to expose the first electrode in a direction opposite to the direction in which the first window 231 exposes the second electrode and the second window 241 exposes the third electrode, and the surface of the first electrode layer 31 is exposed from the back surface of the substrate 41, and therefore, the degree of freedom in designing the area of the third window 211 is higher, which can be advantageous in optimizing the area of the monitor electrode 1, thereby improving the measurement sensitivity of the monitor electrode 1 and reducing the base current.

In this embodiment, in step S600, as shown in fig. 10d, after the third window 211 is formed, the first sacrificial layer 413 and the substrate 41 may be removed by etching the first sacrificial layer 413. For example, when the material of the first sacrificial layer 413 is aluminum, an aluminum etchant may be used to remove the first sacrificial layer 413. This allows the substrate 41 to be removed without damaging the monitoring electrode 1, thereby obtaining the monitoring electrode 1.

In some examples, there may be multiple monitoring electrodes 1 fabricated on one substrate 41, and dicing may be performed using a dicing saw to form a single monitoring electrode 1.

In some examples, if the first electrode layer 31, the second electrode layer 32, and the third electrode layer 33 are, for example, Ti — Pt — Ti structures, the monitoring electrode 1 from which the substrate 41 is removed may be treated with hydrofluoric acid (HF) to etch away the titanium metal layer on the surface. Therefore, the first electrode, the second electrode, the third electrode, the first bonding pad, the second bonding pad and the third bonding pad with better conductivity can be formed on the surface of the electrode layer exposed by the window and the channel.

In this embodiment mode, the low resistance layer 321 is formed on the electrode surface of the second electrode layer 32 located in the first window 231. Specifically, the low resistance layer 321 may be formed by plating, spin coating, evaporating or sputtering one of platinum ash, platinum black, or a combination thereof on the surface of the second electrode. In this case, it is possible to facilitate formation of the low resistance layer 321 having granular sensation. Thereby, the impedance of the electrode surface of the second electrode layer 32 located at the first window 231 can be reduced, and at the same time, the contact area of the sensitive substance 322 responsive to the analyte and the electrode surface can be increased.

In this embodiment, the analyte-responsive sensitive substance 322 may be added to the electrode surface of the second electrode layer 32 located in the first window 231 by means of dropping, sputtering, or the like. In the blood glucose monitoring electrode, the sensitive substance 322 responding to the analyte may be glucose oxidase or glucose dehydrogenase. In other examples, the analyte-responsive sensing substance 322 may vary according to the type of the monitoring electrode and the application scenario, for example, in a uric acid monitoring electrode, the analyte-responsive sensing substance 322 may be selected from the group of uricases, and in a cholesterol monitoring electrode, the analyte-responsive sensing substance 322 may be selected from the group of cholesterol oxidases.

In the present embodiment, the biocompatible coating 111 may be formed outside the detection end 11 of the monitoring electrode 1 to which the analyte-responsive sensitive substance 322 is added.

While the present disclosure has been described in detail in connection with the drawings and examples, it should be understood that the above description is not intended to limit the disclosure in any way. Those skilled in the art can make modifications and variations to the present disclosure as needed without departing from the true spirit and scope of the disclosure, which fall within the scope of the disclosure.

Claims

1. A monitoring electrode for physiological parameters, characterized in that,

the method comprises the following steps:

a base layer having a front side and a back side opposite the front side;

a first electrode layer disposed on the front side of the substrate layer having a first predetermined pattern;

a first insulating layer disposed on the first electrode layer and having a first channel exposing the first electrode layer;

a second electrode layer disposed on the first insulating layer, having a second predetermined pattern;

a second insulating layer disposed on the second electrode layer and having a first window and a second channel exposing the second electrode layer;

a third electrode layer disposed on the second insulating layer and having a third predetermined pattern; and

a third insulating layer disposed on the third electrode layer and having a second window and a third channel exposing the third electrode layer,

wherein a third window exposing the first electrode layer is formed on the back surface of the substrate layer.

2. The monitoring electrode of claim 1,

the first via penetrates to a surface of the third insulating layer to expose the first electrode layer, the second via penetrates to a surface of the third insulating layer to expose the second electrode layer, and the first window penetrates to a surface of the third insulating layer to expose the second electrode layer.

3. The monitoring electrode of claim 1,

the area of the third window is not smaller than that of the first window.

4. The monitoring electrode of claim 1,

the monitoring electrode has a detection end and a connection end, and the first window, the second window, and the third window are formed at the detection end.

5. The monitoring electrode of claim 1,

the first electrode layer, the second electrode layer, and the third electrode layer are not connected to each other.

6. The monitoring electrode of claim 1 or 4,

and a sensitive substance which responds to the analyte is arranged on the surface of the second electrode layer, which is positioned on the first window.

7. The monitoring electrode of claim 6,

the detection end is provided with a biocompatible coating.

8. The monitoring electrode of claim 4,

the connecting end is of a tridentate structure, and the first channel, the second channel and the third channel are respectively located on three branches of the tridentate structure.

9. The monitoring electrode of claim 4,

the connecting end is in a long strip shape, and the first channel, the second channel and the third channel are arranged along the length direction of the connecting end.

10. The monitoring electrode of claim 4,

in the first passage, a solder layer is formed.

11. A method for preparing a monitoring electrode of physiological parameters is characterized in that,

the method comprises the following steps:

(a) preparing a substrate having a front surface and a back surface, and forming a base layer on the front surface of the substrate;

(b) forming a first electrode layer having a first predetermined pattern on the base layer, and then forming a first insulating layer;

(c) forming a second electrode layer having a second predetermined pattern on the first insulating layer, and then forming a second insulating layer;

(d) forming a third electrode layer having a third predetermined pattern on the second insulating layer, and then forming a third insulating layer;

(e) forming a patterned mask layer on the third insulating layer and etching the patterned mask layer to form a first window on the second electrode layer and a second window on the third electrode layer; and is

(f) And patterning and etching the back surface of the substrate to form a third window on the base layer.

12. The method according to claim 11,

in the step (a), a first sacrificial layer is formed between the front surface of the substrate and the base layer, and the first sacrificial layer is patterned.

13. The method according to claim 11,

prior to step (c), the first insulating layer is further patterned and a through hole communicating with the first electrode layer is formed, and in step (c), a soldering layer connected to the first electrode layer is further formed in the through hole.

14. The method according to claim 11,

in step (e), a first channel is further formed on the first electrode layer, a second channel is formed on the second electrode layer, and a third channel is formed on the third electrode layer.

15. The method according to claim 12,

in the step (f), further comprising removing the first sacrificial layer and the substrate by etching the first sacrificial layer after forming the third window.

16. The method according to claim 11,

in the step (b), the first electrode layer is formed by forming a patterned second sacrificial layer on the base layer, and peeling off the second sacrificial layer after forming a metal layer.

17. The method according to claim 11,

and a low resistance layer is formed on the surface of the second electrode layer, which is positioned on the first window.

18. The method of claim 17,

the low resistance layer is formed by plating one of platinum ash, platinum black, or a combination thereof on the surface of the electrode.

19. The method according to claim 11,

composite dielectric films including a silicon dioxide layer and a silicon nitride layer stacked in this order are formed on the front surface and the back surface of the substrate, respectively.

20. The method according to claim 19,

in step (f), the silicon nitride layer on the back surface of the substrate is patterned and etched, and etched to the surface of the first electrode layer, thereby forming the third window.