WO2022246983A1

WO2022246983A1 - Implantable probe and implantable sensor

Info

Publication number: WO2022246983A1
Application number: PCT/CN2021/105736
Authority: WO
Inventors: 汪远; 柏志飞; 陆辉; 褚浩宇
Original assignee: 南京微纳科技研究院有限公司
Priority date: 2021-05-26
Filing date: 2021-07-12
Publication date: 2022-12-01
Also published as: CN115399760A

Abstract

An implantable probe (100), comprising a light guide unit (110), a polymer unit layer (120), indicator molecules (130) and a porous layer (160); the light guide unit (110) is used to transmit excitation light or indicator molecule (130) signal light; the polymer unit layer (120) is a hydrophilic material layer or an amphiphilic material layer, and the polymer unit layer (120) is disposed at an outer side of the light guide unit (110); the indicator molecules (130) are each used to bind to an analyte and generate indicator molecule (130) signal light, and the indicator molecules (130) are disposed within the polymer unit layer (120); the porous layer (160) is used to provide biocompatibility and mechanical strength, and the porous layer (160) is disposed at an outer side of the polymer unit layer (120). An implantable sensor, comprising the implantable probe (100), a light source (200) and a detector (300); the light source (200) is used to provide excitation light for the implantable probe (100); and the detector (300) is used to receive indicator molecule (130) signal light generated by the implantable probe (100). The service life of the implantable probe (100) in the body is relatively long, thereby reducing the frequency of sensor replacement and usage costs for users.

Description

Implantable Probes and Implantable Sensors

This application claims priority to a Chinese patent application with application number 202110576544.2 and application title "Implantable Probe and Implantable Sensor" filed with the China Patent Office on May 26, 2021, the entire contents of which are hereby incorporated by reference In this application.

technical field

The present application relates to the field of substance detection, in particular to an implanted probe and an implanted sensor.

Background technique

At present, there are many sensors on the market that can perform qualitative and quantitative detection of substances, and the above-mentioned sensors can be used to analyze the presence or concentration of analytes in solids, liquids or gases. In the field of biological detection, the traditional way to analyze whether there is a certain analyte in the body fluid in the living body is usually to extract the body fluid out of the body for analysis.

With the advancement of science and technology, an implantable or semi-implantable sensor is disclosed in the related art. The implantable or semi-implantable sensor can be implanted under the epidermis of a living body to detect whether there is a certain analyte or The concentration of a certain analyte, which facilitates real-time monitoring of the health status of the living body.

However, the implantable or semi-implantable sensors in the related art generally use enzyme electrodes for sensing. Due to the influence of enzyme biological activity, the service life of the probe in the living body is short (generally 7-14 days). The replacement frequency is faster, and the user's use cost is higher.

Contents of the invention

In order to overcome the above-mentioned defects in the prior art, the purpose of the present application is to provide an implantable probe and an implantable sensor. The implantable sensor of the present application has a long service life in the living body, thus reducing the replacement of the sensor. Frequency and user cost of use.

An embodiment of the present application provides an implantable probe, comprising:

A light guide unit, the light guide unit is used to conduct excitation light or indicate molecular signal light;

A polymer unit layer, the polymer unit layer is a hydrophilic material layer or an amphoteric material layer, and the polymer unit layer is arranged outside the light guide unit;

Indicator molecules, the indicator molecules are used to combine with the analyte, and generate signal light of the indicator molecules under the action of the excitation light, and the indicator molecules are arranged in the polymer unit layer;

a porous layer, the porous layer has a porous structure inside, used to provide the channel for the analyte to enter the polymer unit layer, the porous layer is used to provide biocompatibility, and the porous layer is also used to provide mechanical The strength protects the polymer unit layer inside it, and the porous layer is provided on the outside of the polymer unit layer.

As described above for the implantable probe, optionally, the material of the light guide unit includes quartz or polymer material.

As for the above-mentioned implantable probe, optionally, in a direction perpendicular to the axial direction of the light guide unit, the cross section of the light guide unit is circular, rectangular or triangular; the diameter of the cross section of the light guide unit or The maximum diagonal length of the section of the light guide unit is 20-150 μm.

As described above for the implantable probe, optionally, the polymer unit layer is a hydrogel layer, and the hydrogel layer includes a polysaccharide hydrogel layer, an acrylic hydrogel layer or a carbamic acid Any one of the ethyl ester hydrogel layers.

As for the above-mentioned implantable probe, optionally, the indicator molecule includes any one of crown ether derivatives, concanavalin, boronic acid derivatives or phthalaldehyde derivatives.

As for the above-mentioned implantable probe, optionally, the color of the porous layer is black, which is used to reduce environmental light infection and shield internal detection light leakage, and the material of the porous layer includes modified chitosan or Modified polyurethane, the modified chitosan includes carbon black modified chitosan or carbon nanotube modified chitosan.

As described above for the implantable probe, optionally, the thickness of the porous layer is 30-150 μm.

The implantable probe as described above, optionally, also includes any one or more layers of an anti-oxidation layer, a modified coating and a reflective layer;

The anti-oxidation layer is disposed between the polymer unit layer and the porous layer;

The modified coating is disposed on the outside of the porous layer;

The reflective layer is located at the end face of the light guide unit.

As described above for the implantable probe, optionally, the anti-oxidation layer is a noble metal layer, and the material of the noble metal layer includes platinum or palladium.

As for the above-mentioned implantable probe, optionally, the anti-oxidation layer is a polymer-wrapped noble metal particle layer.

As described above for the implantable probe, optionally, the anti-oxidation layer has a thickness of 10 μm.

As described above for the implantable probe, optionally, the modified coating is a modified heparin coating.

As described above for the implantable probe, optionally, the reflective layer is a metal film, and the material of the metal film includes silver, aluminum or platinum.

As described above for the implantable probe, optionally, along the axial direction of the light guide unit, the reflective layer has a thickness of 5-15 μm.

As for the above-mentioned implantable probe, optionally, any two adjacent layers are connected by chemical means or physical means.

Another embodiment of the present application provides an implantable sensor, including a light source, a detector, and any implantable probe as described above, the light source is used to emit excitation light to the implantable probe, the The detector is used for receiving the signal light of the implanted probe.

For the above-mentioned implantable sensor, optionally, the light source includes an array light source or a light emitting diode light source, and the light emitted by the light source has a wavelength of 200-1000 nm.

As for the implantable sensor described above, optionally, the detector includes a photodiode or a spectrometer.

The application provides an implanted probe and an implanted sensor. The implanted probe includes a photoconductive unit, a polymer unit layer, indicator molecules and a porous layer. The photoconductive unit is used to conduct excitation light or indicator molecular signal light; the polymer The unit layer is a hydrophilic material layer or an amphoteric material layer, and the polymer unit layer is arranged on the outside of the light guide unit; the indicator molecule is used to combine with the analyte, and the indicator molecule signal light is generated under the action of the excitation light. In the object unit layer; the porous layer has a porous structure inside, which is used to provide a channel for the analyte to enter the polymer unit layer, and the porous layer is also used to provide biocompatibility and mechanical strength, and the porous layer is arranged on the outside of the polymer unit layer. In the present application, the light guide unit is set to transfer the excitation light to the indicator molecules in the polymer unit layer; the polymer unit layer is hydrophilic, allowing the analyte in the living body fluid to enter, thereby specifically combining with the indicator molecules; the present application Compared with the enzyme electrode in the related art, the indicator molecule has stable chemical properties and has no biological activity, so it can exist in the living body for a longer time, thereby prolonging the service life of the implanted sensor and reducing the replacement of the sensor Frequency and user cost of use.

Description of drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings that need to be used in the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description These are some embodiments of the present application. Those skilled in the art can also obtain other drawings based on these drawings without creative work.

Figure 1 shows a schematic cross-sectional view of an implantable probe provided by an embodiment of the present application;

FIG. 2 is a schematic structural diagram of an implantable sensor provided by an embodiment of the present application.

Reference signs:

100-implantable probe; 110-light guide unit; 120-polymer unit layer; 130-indicator molecule; 140-modified coating; 150-anti-oxidation layer; 160-porous layer; 170-reflection layer;

200 - light source;

300 - Detector.

Detailed ways

In order to make the purposes, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments It is a part of the embodiments of this application, not all of them.

Based on the embodiments in this application, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the scope of protection of this application. In the case of no conflict, the following embodiments and features in the embodiments can be combined with each other.

In the description of the present application, it should be understood that the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", " Back", "Left", "Right", "Vertical", "Horizontal", "Top", "Bottom", "Inner", "Outer", "Clockwise", "Counterclockwise", "Axial" , "radial", "circumferential" and other indicated orientations or positional relationships are based on the orientations or positional relationships shown in the drawings, and are only for the convenience of describing the application and simplifying the description, rather than indicating or implying the referred device or Elements must have certain orientations, be constructed and operate in certain orientations, and thus should not be construed as limiting the application.

In this application, terms such as "installation", "connection", "connection" and "fixation" should be interpreted in a broad sense, for example, it can be a fixed connection or a detachable connection, unless otherwise clearly specified and limited. , or integrated; it can be directly connected or indirectly connected through an intermediary, it can be the internal communication of two elements or the interaction relationship between two elements. Those of ordinary skill in the art can understand the specific meanings of the above terms in this application according to specific situations.

It should be noted that in the description of this application, the terms "first" and "second" are only used to describe different components conveniently, and should not be understood as indicating or implying a sequence relationship, relative importance, or implicit indication The number of technical characteristics. Thus, features defined as "first" and "second" may explicitly or implicitly include at least one of these features.

An implantable or semi-implantable sensor is disclosed in the related art. The implantable or semi-implantable sensor can be implanted under the epidermis of a living body to detect whether there is a certain analyte or the concentration of a certain analyte in the living body fluid , so as to facilitate real-time monitoring of the health status of the living body. However, the implantable or semi-implantable sensors in the related art generally use enzyme electrodes for sensing. Due to the influence of enzyme biological activity, the service life of the probe in the living body is short (generally 7-14 days). The replacement frequency is faster, and the user's use cost is higher.

Host-guest chemistry refers to the chemistry of studying complexes with certain structural characteristics formed by two or more molecules through non-covalent bonds. At present, an implantable sensor based on the principle of host-guest chemical specific recognition causing changes in optical properties (such as: optical absorption, fluorescence effect, phosphorescence effect, Raman effect, etc.) can solve the problem of enzyme electrode life. After the probe is inserted into the medium where the analyte is located, the indicator molecule will specifically bind to the analyte, resulting in a physical or chemical change, and under the action of the incident light, the signal light of the indicator molecule will be generated, and the detector will be used to detect the signal after the change light so that the presence or concentration of an analyte can be determined. In view of this, the present application aims to provide an implantable sensor with a long service life in the living body.

The content of the present application will be described in detail below in conjunction with the accompanying drawings, so that those skilled in the art can understand the content of the present application in more detail.

Embodiment one

FIG. 1 is a schematic cross-sectional view of an implantable probe provided by an embodiment of the present application; please refer to FIG. 1 . This embodiment provides an implantable probe 100, including:

The light guide unit 110 is used for conducting excitation light or indicating molecular signal light, that is, the light guide unit 110 is used for propagating light inside the light guide unit 110 to realize the transmission of light signals. The material of the light guide unit 110 may be quartz or polymer material.

The polymer unit layer 120, the polymer unit layer 120 is a hydrophilic material layer or an amphoteric material layer (that is, a film layer with both hydrophilicity and hydrophobicity), and the hydrophilic polymer unit layer 120 can be used to make the living body The water-soluble analytes can smoothly enter the interior of the polymer unit layer 120 . In practical applications, the hydrophilicity of the polymer unit layer 120 can also be adjusted by introducing another monomer, so as to improve the ability of the water-soluble analyte to uniformly disperse in the polymer unit layer, and control the analyte entering the polymer unit layer 120. To avoid excessive concentration of the analyte, indicating the occurrence of molecular "saturation". Specifically, the hydrophilicity of the polymer unit layer 120 can be adjusted by introducing monomers such as 2-hydroxyethyl methacrylate (HEMA) and N-vinylpyrrolidone (NVP).

The polymer unit layer 120 is arranged on the outside of the light guide unit 110, so that the excitation light in the light guide unit 110 can enter the polymer unit layer 120 from any position, or the indicator molecular signal light can be transmitted from any position of the polymer unit layer 120 into the light guide unit 110 . Optionally, the polymer unit layer 120 and the light guide unit 110 may be connected chemically or physically. For example, the molecules in the polymer unit layer 120 can be connected with the molecules in the light guide unit 110 by means of covalent bonding, or the polymer unit layer 120 can be coated on the light guide unit 110 by means of adhesive connection. outside. It is connected by chemical or physical means to ensure that it will not fall off during use, especially in the process of high-speed implantation and extraction from the living body, the frictional force is relatively large, and the above connection method can ensure that the polymer unit The shapes of the layer 120 and the light guide unit 110 are relatively stable, and phenomena such as detachment and falling will not occur.

indicator molecule 130, the indicator molecule 130 is used to combine with the analyte and generate indicator molecule signal light, when the analyte binds to its specific indicator molecule 130, it will cause the indicator molecule 130 to change in physical or chemical properties, thereby Under the action of the excitation light, the indicator molecule signal light is generated, and the presence or concentration of the analyte can be determined through the change of the signal light before and after the indicator molecule combines with the analyte. The indicator molecule 130 needs to combine with the analyte to produce a reversible optical signal change. The indicator molecule 130 is arranged in the polymer unit layer 120, and the type of the indicator molecule 130 can be selected according to the type or concentration of the analyte. Compared with the poor biological stability of enzyme electrodes in the related art, the indicator molecule 130 in this embodiment is a non-biologically active substance with stable chemical properties, so the indicator molecule 130 can exist in the living body for a long time, making implantation The sensor has a longer service life. In this embodiment, the indicator molecule 130 includes any one of crown ether derivatives, concanavalin, boric acid derivatives or o-phthalaldehyde derivatives. Of course, the indicator molecule 130 can also use other suitable substances. This application is here No longer. Specifically, crown ether derivatives can be used when measuring potassium ions in body fluids; concanavalin or boric acid derivatives can be used when measuring glucose in body fluids; o-phthalaldehyde derivatives can be used when measuring cholesterol in body fluids things. In this embodiment, the specific indicator molecule 130 is used, and its stability is much higher than that of the enzyme electrode. For example, the service life of the implanted sensor using the enzyme electrode is generally 7-14 days, while the indicator molecule 130 of this embodiment is used. The lifespan of the implanted sensor is generally 90-180 days, which can realize continuous and high-precision measurement of analytes in body fluids.

In this embodiment, the indicator molecules 130 can be arranged in the polymer unit layer 120 by chemical or physical means, for example, the molecules in the polymer unit layer 120 can be connected with the indicator molecules 130 by means of covalent bonding, or , the indicator molecule 130 can be put into the polymer unit layer 120 by encapsulation, encapsulation, embedding and the like.

The porous layer 160 , the porous layer 160 has a porous structure inside, and is used to provide a channel for the analyte to enter the polymer unit layer 120 . The porous layer 160 is used to improve biocompatibility, and the porous layer 160 is also used to provide mechanical strength to protect the polymer unit layer 120 inside; the porous layer 160 is disposed outside the polymer unit layer 120 . Optionally, the porous layer 160 and the polymer unit layer 120 may be connected chemically or physically. For example, the molecules in the porous layer 160 can be connected with the molecules in the polymer unit layer 120 by covalent bonding, or the porous layer 160 can be coated on the polymer unit layer 120 by adhesive connection. outside. It is connected by chemical or physical means to ensure that it will not fall off during use, especially in the process of high-speed implantation and extraction of living organisms, the frictional force is relatively large, and the above connection method can ensure that the porous layer 160 The shape of the polymer unit layer 120 is relatively stable, and phenomena such as desorption and drop will not occur.

Specifically, the polymer unit layer 120 of this embodiment is hydrophilic, and can allow the analyte in the living body fluid to enter, so as to specifically combine with the indicator molecule 130 . After the implantable probe 100 of this embodiment is placed in the living body, the analyte in the living body fluid can be incorporated into the hydrophilic polymer unit layer 120, so that the analyte and the indicator molecule 130 produce a host-guest chemical specific combination , leading to physical or chemical changes in the indicator molecule 130 . The excitation light propagates to the indicator molecule through the light guide unit 110, under the action of the excitation light, the indicator molecule generates signal light, and the presence or concentration of the analyte is determined by the change of the signal light before and after the analyte binds to the indicator molecule.

Compared with the enzyme electrode in the related art, the indicator molecule 130 of this embodiment has stable chemical properties and has no biological activity, so it can exist in the living body for a longer time, thereby prolonging the service life of the implanted sensor and reducing the Probe replacement frequency and user cost.

In a preferred implementation manner, the material of the light guide unit 110 in this embodiment includes any one of quartz, polymethyl methacrylate, polycarbonate or polydimethylsiloxane. According to different use scenarios, the cross-sectional diameter of the light guide unit 110 can be selected from 2-50 mm.

In a preferred embodiment, in the direction perpendicular to the axial direction of the light guide unit 110, the cross-section of the light guide unit 110 in this embodiment can be in a regular shape such as a circle, a rectangle or a triangle. Of course, it is clear to those skilled in the art that , the cross-section of the light guide unit 110 can also be irregular, as long as it can meet the requirements of light transmission.

In a preferred embodiment, in a direction perpendicular to the axial direction of the light guide unit 110 , the diameter of the section of the light guide unit 110 or the maximum diagonal length of the section of the light guide unit 110 in this embodiment is 20-150 μm. More preferably, the diameter of the section of the light guide unit 110 or the maximum diagonal length of the section of the light guide unit 110 is 30-100 µm.

In a preferred embodiment, the polymer unit layer 120 includes a hydrogel layer, and the hydrogel layer may be a hydrogel layer of a polymer network structure, but this embodiment is not limited thereto. The material of the hydrogel layer in this embodiment includes any one of polysaccharide hydrogel materials, acrylic hydrogel materials or urethane hydrogel materials.

Specifically, the above-mentioned polysaccharide hydrogel material includes methyl cellulose or dextran; the above-mentioned acrylic hydrogel material includes acrylamide, methacrylamide, methylol acrylamide or hydroxyethyl acrylate; the above-mentioned Urethane hydrogel materials include polyethylene glycol or diisocyanate.

In a preferred embodiment, the porous layer 160 of this embodiment can be black, which is used to reduce environmental light infection and shield the internal detection of light leakage. The material of the porous layer 160 includes modified chitosan added with black materials, Modified chitosan includes carbon black modified chitosan or carbon nanotube modified chitosan.

In a preferred implementation manner, the thickness of the porous layer 160 in this embodiment is 30-150 μm.

Further, the implantable probe of this embodiment also includes an anti-oxidation layer 150, which is used to catalyze and degrade the oxides produced by the immune reaction, so as to reduce the oxidation effect of the oxides on the indicator molecules 130 and avoid the indicator molecules 130 Deterioration and failure. The anti-oxidation layer 150 is disposed between the polymer unit layer 120 and the porous layer 160 . Optionally, the anti-oxidation layer 150 may be chemically or physically connected to the polymer unit layer 120 and the porous layer 160 . For example, the molecules in the anti-oxidation layer 150 can be connected with the molecules in the polymer unit layer 120 or the molecules in the porous layer 160 by covalent bonding, or the anti-oxidation layer 150 can be connected by adhesive bonding. coated on the outside of the polymer unit layer 120 . It is connected by chemical or physical means to ensure that it will not fall off during use, especially in the process of high-speed implantation and extraction of the living body, the frictional force is relatively large, and the above connection method can ensure that the anti-oxidation layer 150 The shapes of the polymer unit layer 120 and the porous layer 160 are relatively stable, and phenomena such as desorption and falling will not occur.

In a preferred implementation manner, the anti-oxidation layer 150 of this embodiment may be a noble metal layer, specifically, the noble metal material may be platinum or palladium.

In a preferred implementation manner, the anti-oxidation layer 150 of this embodiment may also be a polymer-wrapped noble metal particle layer.

Preferably, the anti-oxidation layer 150 in this embodiment may have a thickness of 10 μm.

In other optional embodiments, the anti-oxidation layer 150 and the porous layer 160 can be integrated into one layer, for example, anti-oxidation molecules can be added in the porous layer 160 to realize the functions of the anti-oxidation layer 150 and the porous layer 160 at the same time. Antioxidant molecules can be arranged in the porous layer 160 by chemical or physical means, for example, the molecules in the porous layer 160 can be connected with the antioxidative molecules by means of covalent bonding, or can be wrapped, covered, The anti-oxidant molecules are put into the porous layer 160 by means of embedding or the like.

Further, the implantable probe 100 of this embodiment also includes a modified coating 140, which is used to improve the ability to resist immune interference, such as resisting the immune reaction and blood coagulation reaction after implantation, so that Improving the detection accuracy of implantable sensors. The modified coating 140 of this embodiment is disposed on the outer side of the porous layer 160 , that is, the outermost side of the implantable probe 100 , so as to provide the implantable probe 100 with an anti-immune function. Optionally, the porous layer 160 and the modified coating 140 may be connected chemically or physically. For example, the molecules in the porous layer 160 can be connected with the molecules in the modified coating 140 by means of covalent bonding, or the modified coating 140 can be coated on the surface of the porous layer 160 by means of adhesive connection. outside. It is connected by chemical or physical means to ensure that it will not fall off during use, especially in the process of high-speed implantation and extraction of living organisms, the frictional force is relatively large, and the above connection method can ensure that the porous layer 160 and The shape of the modified coating 140 is relatively stable, and phenomena such as desorption and falling will not occur.

In a preferred embodiment, the modified coating 140 of this embodiment includes a modified heparin coating, which is covalently bonded to the porous layer 160. The modified heparin coating can reduce the deposition of platelets and blood cells.

Further, this embodiment may further include a reflective layer 170, which is used to reflect the excitation light or indicator molecular signal light, so as to increase the utilization rate of the light source and improve the collection efficiency of the indicator molecular signal light. The reflective layer 170 is located at the end surface of the light guide unit 110 .

In a preferred implementation manner, the reflective layer 170 of this embodiment is a metal film disposed on the end surface of the light guide unit 110, and the material of the metal film includes silver, aluminum or platinum.

In a preferred embodiment, along the axial direction of the light guide unit 110 , the reflective layer 170 has a thickness of 5-15 μm.

In a preferred embodiment, the minimum diameter of the implantable probe 100 in this embodiment is 400 μm, and the entire implantable probe has a small and compact structure, which is basically “non-inductive” for implantation.

Embodiment two

FIG. 2 shows a schematic structural diagram of an implantable sensor provided by an embodiment of the present application; please refer to FIG. 2 . This embodiment provides an implantable sensor, including a light source 200, a detector 300, and the implantable probe 100 as described in Embodiment 1 above. The light source 200 is used to emit excitation light to the implantable probe 100, and the detector 300 is used to The signal light of the implantable probe 100 is received.

Specifically, the implantable sensor of this embodiment can emit excitation light to the implantable probe 100 through the light source 200, and the excitation light is transmitted into the implantable probe 100 through the light guide unit 110, since the implantable probe 100 is located at In vivo, the analyte in the living body fluid can be incorporated into the hydrophilic polymer unit layer 120 , and the combination of the analyte and the indicator molecule 130 will lead to changes in the physical or chemical properties of the indicator molecule 130 . The indicator molecules after the above changes generate indicator molecule signal light under the action of the excitation light, which is transmitted to the detector 300 through the light guide unit 110, and the detector 300 can convert the optical signal into an electrical signal and transmit it to an external processor. The reference data of the analytes in the living body can be pre-stored in the processor, and the real-time data of the analytes in the living body can be obtained after analysis, calculation and comparison by the processor.

In a preferred embodiment, the light source 200 of this embodiment includes an array light source 200 or a light-emitting diode light source 200. In order to make the entire implantable sensor miniaturized and easy to carry, the light source 200 is preferably a light-emitting diode light source, and the light-emitting diode light source can be A filter is provided to filter out unnecessary light, and the optional wave bands are ultraviolet, visible, near-infrared, and mid-infrared. Usually the light source 200 is tuned as a light source with an illumination peak wavelength, and the wavelength of the light emitted by the light source 200 is 200-1000 nm, for example, 254 nm, 365 nm, 800 nm, etc. can be selected.

In a preferred implementation manner, the detector 300 of this embodiment includes a photodiode or a spectrometer. In order to make the entire implantable sensor miniaturized and easy to carry, the detector 300 preferably uses a photodiode.

Since the implantable sensor of this embodiment adopts the implantable probe 100 of the above-mentioned embodiment 1, it can exist in the human body for a long time, thus prolonging the service life of the implantable sensor and reducing the cost of the probe. Replacement frequency and patient cost of use.

Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present application, and are not intended to limit it; although the application has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: It is still possible to modify the technical solutions described in the foregoing embodiments, or perform equivalent replacements for some or all of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the technical solutions of the various embodiments of the present application. scope.

Claims

An implantable probe, characterized in that it comprises:

A light guide unit, the light guide unit is used to conduct excitation light or indicate molecular signal light;

A polymer unit layer, the polymer unit layer is a hydrophilic material layer or an amphoteric material layer, and the polymer unit layer is arranged outside the light guide unit;

Indicator molecules, the indicator molecules are used to combine with the analyte, and generate signal light of the indicator molecules under the action of the excitation light, and the indicator molecules are arranged in the polymer unit layer;

a porous layer, the porous layer has a porous structure inside, used to provide the channel for the analyte to enter the polymer unit layer, the porous layer is used to provide biocompatibility, and the porous layer is also used to provide mechanical The strength protects the polymer unit layer inside it, and the porous layer is provided on the outside of the polymer unit layer.
The implantable probe according to claim 1, wherein the material of the light guiding unit comprises quartz or polymer material.
The implantable probe according to claim 2, characterized in that, in a direction perpendicular to the axial direction of the light guide unit, the cross section of the light guide unit is circular, rectangular or triangular; the cross section of the light guide unit is The diameter or the maximum diagonal length of the cross-section of the light guide unit is 20-150 μm.
The implantable probe according to claim 1, wherein the polymer unit layer is a hydrogel layer, and the hydrogel layer comprises a polysaccharide hydrogel layer, an acrylic hydrogel layer Or any one of the urethane hydrogel layers.
The implantable probe according to claim 1, wherein the indicator molecule comprises any one of crown ether derivatives, concanavalin, boric acid derivatives or o-phthalaldehyde derivatives.
The implantable probe according to claim 1, wherein the color of the porous layer is black, which is used to reduce environmental light infection and shield internal detection light leakage, and the material of the porous layer includes a modified shell polysaccharide or modified polyurethane, and the modified chitosan includes carbon black modified chitosan or carbon nanotube modified chitosan.
The implantable probe according to claim 5, wherein the thickness of the porous layer is 30-150 μm.
The implantable probe according to any one of claims 1-7, further comprising any one or more layers of an anti-oxidation layer, a modified coating, and a reflective layer;

The anti-oxidation layer is disposed between the polymer unit layer and the porous layer;

The modified coating is disposed on the outside of the porous layer;

The reflective layer is located at the end face of the light guide unit.
The implantable probe according to claim 8, wherein the anti-oxidation layer is a noble metal layer, and the material of the noble metal layer includes platinum or palladium.
The implantable probe according to claim 8, wherein the anti-oxidation layer is a layer of noble metal particles wrapped in a polymer.
The implantable probe according to claim 8, wherein the thickness of the anti-oxidation layer is 10 μm.
The implantable probe according to claim 8, wherein the modified coating is a modified heparin coating.
The implantable probe according to claim 8, wherein the reflective layer is a metal film, and the material of the metal film includes silver, aluminum or platinum.
The implantable probe according to claim 8, characterized in that, along the axial direction of the light guide unit, the thickness of the reflective layer is 5-15 μm.
The implantable probe according to claim 8, characterized in that any two adjacent layers are connected chemically or physically.
An implantable sensor, characterized in that it comprises a light source, a detector and the implantable probe according to any one of claims 1-15, the light source is used to emit excitation light to the implantable probe , the detector is used for receiving the signal light of the implanted probe.
The implantable sensor according to claim 16, wherein the light source comprises an array light source or a light emitting diode light source, and the light emitted by the light source has a wavelength of 200-1000 nm.
The implantable sensor of claim 16, wherein the detector comprises a photodiode or a spectrometer.