CN115326891A

CN115326891A - Flexible blood glucose concentration sensor and preparation method thereof

Info

Publication number: CN115326891A
Application number: CN202210858520.0A
Authority: CN
Inventors: 李辉; 张云帆; 陈傲杰; 唐舞阳; 申胜男
Original assignee: Wuhan University WHU
Current assignee: Wuhan University WHU
Priority date: 2022-07-20
Filing date: 2022-07-20
Publication date: 2022-11-11

Abstract

The invention discloses a flexible blood glucose concentration sensor and a preparation method thereof, wherein the flexible blood glucose concentration sensor comprises a flexible substrate, a microneedle array, a micro-reaction tank and a detection circuit, the microneedle array, the micro-reaction tank and the detection circuit are arranged on the flexible substrate, when in preparation, a flexible porous microneedle array is prepared by mixing saline citric acid particles with PDMS (polydimethylsiloxane) and pouring, the substrate of the microneedle array is used as the flexible substrate, a groove is prepared or reserved on the flexible substrate and used as the micro-reaction tank, then capacitor plates are respectively printed on two slopes of the groove by ink-jet printing, inductance coils connected with the two capacitor plates are printed on the periphery of the groove to complete the preparation of an LC resonance circuit, and then gel containing glucolase is injected into the micro-reaction tank and used as a dielectric material; and packaging the LC resonance circuit to obtain the flexible blood glucose concentration sensor. The invention utilizes the porous micro-needle to suck the tissue fluid and transmit the tissue fluid to the micro-reaction tank for detecting the blood sugar concentration. The invention has simple structure, stable and reliable process, and the obtained sensor has good flexibility and can be worn for long-term detection.

Description

Flexible blood glucose concentration sensor and preparation method thereof

Technical Field

The invention belongs to the technical field of sensors, relates to a blood glucose concentration sensor, and particularly relates to a flexible blood glucose concentration sensor and a preparation method thereof.

Background

With the improvement of living standard of people, diabetes gradually develops into one of common chronic diseases, and for the diabetics, the continuous monitoring of the blood sugar concentration can accurately display the change condition of blood sugar, guide the dietary activity and medication of the diabetics, and greatly reduce the social medical cost caused by frequent hospitalization of the diabetics; but also can reduce the use of the self-checking kit of blood sugar concentration and reduce the pain and mental stress of patients. Therefore, the tissue fluid continuous monitoring has wide development prospect for the biomedical equipment of the next generation.

As an emerging technology in the field of biomedical engineering, the micro-needle can acquire biological information in a minimally invasive mode, the length of the micro-needle is usually not more than 1mm, and the diameter of the micro-needle is not more than 500 micrometers, so that the micro-needle does not contact blood vessels and nerve endings, and further does not cause bleeding and pain in the detection process. Among different types of microneedles, the porous microneedles are convenient for forming fluid channels and have the characteristic of diversified raw materials, so that the porous microneedles become a research hotspot in the field of biological information monitoring.

At present, the traditional blood glucose concentration sensor is generally made of rigid materials such as metal or semiconductor, which can not be tightly attached to the surface of the skin, but can be easily broken due to the movement of the human body in the measurement process; meanwhile, the new biocompatible flexible material has the defects of insufficient mechanical strength, difficulty in puncturing the skin and incapability of realizing long-term stable application of the sensor on the skin surface of a human body; in addition, the existing microneedle is mainly matched with glucose test paper for detection, the precision and the reliability of the detection mode are not high, and the in-situ continuous monitoring of the blood glucose concentration is difficult to realize.

Therefore, there is an ongoing need for a novel blood glucose sensor with flexibility and biocompatibility, which can realize in-situ continuous monitoring of blood glucose concentration and meet the requirements of the biomedical engineering field.

Disclosure of Invention

Aiming at the defects of easy fracture, low detection precision, incapability of realizing in-situ continuous monitoring and the like of the conventional blood glucose concentration sensor, the invention provides the flexible blood glucose concentration sensor and the preparation method thereof, so that various defects of the original materials and processes are broken through, and the in-situ continuous monitoring of the blood glucose concentration is effectively realized.

In order to solve the technical problem, the technical scheme adopted by the invention comprises the following steps:

a flexible blood glucose concentration sensor, comprising:

the flexible substrate is made of flexible insulating materials which can be bent but not extended and is used as a supporting base body of the whole sensor;

the micro-reaction tank is arranged on the flexible substrate and is used for containing gel containing glucolase;

the detection circuit is an LC resonance circuit formed by connecting two capacitor plates through an inductance coil, the two capacitor plates are oppositely arranged in the micro-reaction tank, and gel containing glucolase is used as a dielectric layer;

the micro-needle array comprises a plurality of porous micro-needles arranged on the flexible substrate and used for puncturing the epidermis, and the porous structures of the porous micro-needles are communicated with the micro-reaction tank through micro-channels; conveying the tissue fluid absorbed after the epidermis is punctured into a micro-reaction tank by utilizing a capillary principle; glucose in the tissue fluid is decomposed by glucolase to change the dielectric property of the dielectric layer, so that the corresponding relation between the resonance frequency of the LC resonance circuit and the glucose concentration in the tissue fluid is established.

Furthermore, the micro-reaction tank is at least provided with two opposite slopes, the LC resonance circuit is prepared on the flexible substrate through an ink-jet printing technology, the two capacitor plates are printed on the two slopes, the inductance coil is a spiral coil printed on the flexible substrate around the micro-reaction tank, the inner side end of the spiral coil is directly connected with the first capacitor plate, and the outer side of the spiral coil is connected with the second capacitor plate after being isolated by the insulating layer.

When the micro-reaction device is used, one side of the flexible substrate, which is provided with the micro-needle array, is covered on the skin of a human body, and the tissue fluid absorbed by the porous micro-needles of the flexible substrate after the porous micro-needles pierce the epidermis is conveyed into the micro-reaction pool; glucose in interstitial fluid is decomposed by glucolase to generate micro-current, so that the slope capacitor is partially short-circuited, the dielectric property of the dielectric layer is changed, and the corresponding relation between the resonance frequency of the LC resonance circuit and the glucose concentration in the interstitial fluid is established. The frequency of the LC resonance circuit is detected wirelessly through a vector network analyzer, filtering analysis is carried out, the resonance frequency of the LC resonance circuit and a response curve of the blood glucose concentration in tissue fluid are calibrated according to an experimental result, the blood glucose concentration is fed back in real time, and the in-situ continuous monitoring of the blood glucose concentration is realized.

Furthermore, the surface of the porous microneedle is coated with glycosaminoglycan for strengthening treatment, the glycosaminoglycan is non-toxic and harmless, the biocompatibility is good, the strength of the porous microneedle can be greatly improved, the porous microneedle can easily puncture the epidermis of a human body, and after puncture, the glycosaminoglycan is automatically degraded under the action of human tissue fluid, so that the porous microneedle becomes soft and can deform along with the action of the skin of the human body, and therefore, the porous microneedle is not easy to drop off and break, and long-term wearing monitoring becomes possible.

The invention also provides a preparation method of the flexible blood glucose concentration sensor, which is characterized by comprising the following steps:

step 1, preparing a microneedle array on the lower surface of a flexible substrate or preparing the microneedle array through a microneedle mould, and taking a substrate of the microneedle array as the flexible substrate;

step 2, preparing grooves with paired slopes on the upper surface of the flexible substrate to serve as micro-reaction pools, or reserving corresponding grooves through a micro-needle mold to serve as the micro-reaction pools, wherein porous structures of porous micro-needles are communicated with the micro-reaction pools through micro-channels;

step 3, soaking the prepared microneedle array in a glycosaminoglycan solution, and then drying to obtain a glycosaminoglycan coating reinforced microneedle array;

step 4, performing hydrophilic modification treatment on the flexible substrate;

step 5, preparing an LC resonance circuit on the hydrophilic modified flexible substrate through ink-jet printing, wherein two capacitor plates are respectively printed on two opposite slopes of the micro-reaction tank;

step 6, injecting gel containing glucolase as a dielectric material into the micro-reaction pool;

and 7, preparing a flexible protective layer for wrapping and protecting the LC resonance circuit on the flexible substrate to finish the preparation of the flexible blood glucose concentration sensor.

Further, the LC resonant circuit of step 5 is prepared as follows:

printing a second capacitor plate and an outer lead connected with the capacitor plate;

then preparing an insulating layer on the outer lead and exposing the outer end part of the outer lead;

preferably, a spiral coil surrounding the micro-reaction cell is printed on the flexible substrate and the insulating layer, the inner end of the spiral coil is connected with the first capacitor plate through an inner lead, and the outer end of the spiral coil is connected with the outer end of the outer lead.

The invention also provides the application of the flexible blood glucose concentration sensor, which is matched with a vector network analyzer to use the frequency of the wireless detection LC resonance circuit, carry out filtering analysis and feed the blood glucose concentration back to a patient in real time so as to realize the in-situ continuous monitoring of the blood glucose concentration.

According to the preparation method of the sensor, the LC resonance circuit is printed on the back of the microneedle substrate by using an ink-jet printing technology, so that the use of the traditional semiconductor processing technology is avoided, the technology is simplified, the operation difficulty is reduced, the problems of etching liquid sputtering pollution and the like are solved, meanwhile, a design drawing can be drawn by using CAD software, and the structural parameters of the sensor can be adjusted according to actual conditions so as to meet the requirements under different working conditions. The selected microneedle material has good flexibility, ductility, electrical insulation and biocompatibility, and meets the requirement of personalized installation. The selected dielectric material has excellent dielectric property, can feed back the change of the relative dielectric constant in real time to the change of the glucose concentration in the environment, and ensures the reliability and high sensitivity of monitoring.

Compared with the prior art, the invention has the following beneficial effects:

1. the flexible blood glucose concentration sensor provided by the invention has the advantages of simple structure, flexibility, long-term stable application and the like, can be processed into various shapes, and the glycosaminoglycan with the reinforcing effect is coated on the porous microneedle prepared from the PDMS mixed with the citric acid particles, so that the porous microneedle has enough strength to puncture the human epidermis, and after puncture, the glycosaminoglycan is biodegraded under the action of human tissue fluid, the flexibility of the porous microneedle is recovered, and the problem that the traditional microneedle is easy to break due to human motion is solved.

2. The flexible blood glucose concentration sensor provided by the invention processes a detection circuit on the surface of the microneedle substrate, and designs a packaging structure for sealing based on the special biological environment of human skin, thereby solving the problems of low detection precision, poor reliability and the like caused by the detection of the existing microneedle by using test paper.

3. The flexible blood glucose concentration sensor provided by the invention is matched with the vector network analyzer to analyze the LC circuit resonance frequency signal, so that the blood glucose concentration can be fed back in real time, and the problem of in-situ continuous detection of the blood glucose concentration is solved.

4. The preparation method of the flexible blood glucose concentration sensor provided by the invention has the characteristics of low cost, environmental protection and no toxicity, auxiliary materials are not needed in the preparation process, a special process of using large-scale equipment is not involved, a reagent with high toxicity is not adopted, and all consumables are used in a finished product, so that the utilization rate of the materials reaches 100%.

Drawings

FIG. 1 is a longitudinal cross-sectional view of a flexible blood glucose concentration sensor in an embodiment of the present invention.

Fig. 2 top view of a flexible blood glucose concentration sensor without a flexible protective cover in an embodiment of the present invention.

Fig. 3 a transverse cross-sectional view of a flexible protective cover flexible blood glucose concentration sensor at a micro-reaction cell in an embodiment of the present invention.

The attached figure illustrates that 1-flexible substrate, 2-microneedle array, 21-porous microneedle, 22-glycosaminoglycan coating, 23-microchannel, 3-detection circuit, 31-first capacitance plate, 32-second capacitance plate, 33-spiral coil, 34-insulating layer, 35-outer lead, 4-flexible protective layer, 5-micro reaction tank, 51-slope, 52-gel.

Detailed Description

The device of the present invention will be described in detail with reference to the accompanying drawings.

As shown in FIG. 1, the present invention provides a flexible blood glucose concentration sensor comprising

The flexible substrate 1 is made of flexible insulating materials which can be bent but not extended and is used as a supporting base body of the whole sensor;

a micro-reaction tank 5 arranged on the flexible substrate 1 and used for containing gel 52 containing glucolase;

the detection circuit 3 is an LC resonance circuit formed by connecting two capacitor plates through an inductance coil, the two capacitor plates are oppositely arranged in the micro reaction tank 5, and gel 52 containing glucolase is used as a dielectric layer;

the micro-needle array 2 comprises a plurality of porous micro-needles 21 which are arranged on the flexible substrate 1 and used for puncturing the epidermis, and the porous structures of the porous micro-needles 21 are communicated with the micro-reaction tank 5 through micro-channels 23; the tissue fluid absorbed after the epidermis is punctured is conveyed into a micro-reaction tank 5 by utilizing the capillary principle; glucose in the tissue fluid is decomposed by glucolase to change the dielectric property of the dielectric layer, so that the corresponding relation between the resonance frequency of the LC resonance circuit and the glucose concentration in the tissue fluid is established.

As a preferred embodiment, the micro reaction cell 5 has at least two opposite slopes 51, the LC resonant circuit is prepared on the flexible substrate 1 by inkjet printing technology, two capacitor plates are printed on the two slopes 51, and the two capacitor plates and the gel 52 containing glucolase therebetween form a slope capacitor; the inductance coil is a spiral coil 33 printed on the flexible substrate 1 around the micro reaction tank 5, the inner side end of the spiral coil 33 is directly connected with the first capacitor plate 31, and the outer side of the spiral coil 33 is isolated by an insulating layer 34 and then connected with the second capacitor plate 32.

The principle of measuring the blood glucose concentration of the invention is as follows: the flexible substrate 1 of the sensor is manufactured into a corresponding size according to specific requirements, the flexible substrate is attached to the surface of human skin, the glycosaminoglycan coating 22 enables the porous microneedle 21 to have enough mechanical strength to penetrate through the surface layer of the skin, and after the porous microneedle 21 enters the subcutaneous part, the glycosaminoglycan coating 22 is degraded and decomposed through human tissue fluid, so that the porous microneedle 21 prepared from PDMS recovers flexibility; after the microneedle array 2 is stably attached, microneedles are elastically deformed by physical pressing, a porous structure of the porous microneedles 21 absorbs tissue fluid through the capillary principle and is conveyed into the micro-reaction tank 5 through the micro-channel 23, glucose in the tissue fluid is decomposed by glucolase in the micro-reaction tank 5 and generates micro-current, so that the relative dielectric constant of a liquid environment in the tank is changed, further a slope capacitor formed by two capacitor plates is changed, the frequency change condition of the LC resonance circuit is wirelessly and continuously detected through an external vector network analyzer, filtering analysis is carried out, the resonance frequency of the LC resonance circuit and a blood glucose concentration response curve in the tissue fluid are calibrated according to an experimental result, the blood glucose concentration is fed back in real time, and in-situ continuous monitoring of the blood glucose concentration is realized.

As a preferred embodiment, a flexible protective layer 4 is packaged above the LC resonant circuit of the flexible substrate 1, and the flexible protective layer 4 may be made of the same material as the flexible substrate 1, and may be made by inkjet printing or coating.

As a preferred embodiment, the spiral coil 33 is any one of a circular spiral coil, a rectangular spiral coil and a regular polygonal spiral coil.

Further preferably, the flexible protective layer 4 is provided with a plurality of air holes, so that the body tissue fluid can be continuously absorbed by the porous micro-needle 21 through the capillary effect and can be conveyed into the micro-reaction tank 5, and the continuous monitoring can be realized.

As a preferred embodiment, the thickness of the flexible substrate 1 is 0.5-3mm, and most preferably 1.5mm.

As a preferred embodiment, the material of the flexible substrate 1 and the micro-needle is Polydimethylsiloxane (PDMS), but is not limited thereto.

As a preferred embodiment, the thickness of the LC resonance circuit based on ink-jet printing processing is 100-300nm, and is optimally about 200nm, so that the thickness of the connecting circuit can be ignored in the preparation and packaging process, adjacent flexible materials can be directly superposed to realize packaging, and additional packaging structures such as other adhesives are not needed. The ink for ink-jet printing is preferably nano-silver ink.

As a preferred embodiment, the porous microneedle 21 is a flexible porous microneedle, and the surface of the flexible porous microneedle is reinforced by coating glycosaminoglycan.

As a preferred embodiment, the porous microneedle 21 has a tip with a cone angle of 20-40 ° and a porosity of 40-70%.

Further preferably, the microneedles are pyramidal microneedles 1200 μm long and 620 μm wide with a tip angle set at 30 °, tip spacing set at 1mm, and a porosity of 60%.

As a preferred embodiment, the surface of the porous microneedle 21 is coated with glycosaminoglycan for reinforcement treatment, the glycosaminoglycan is non-toxic and harmless and has good biocompatibility, the strength of the porous microneedle 21 can be greatly improved, the porous microneedle can easily puncture the epidermis of a human body, and after puncture, the glycosaminoglycan is automatically degraded under the action of human tissue fluid, so that the porous microneedle 21 becomes soft and can deform along with the action of the skin of the human body, and therefore, the porous microneedle is not easy to drop out and break, and long-term wearing monitoring becomes possible.

As a preferred embodiment, the gel 52 for carrying the glucolase is a PVA gel and/or a PLA gel.

As a preferred embodiment, the material of the insulating layer 34 separating the second capacitor plate 32 and the spiral coil 33 is Polydimethylsiloxane (PDMS) and/or polytrimethylene carbonate (PTMC), but is not limited thereto.

As a preferred embodiment, the ramp 51 is a capacitor plate having an area of 10-100mm ² 。

The invention also provides a preparation method of the flexible blood glucose concentration sensor, which comprises the following steps:

step 1, preparing a microneedle array 2 on the lower surface of a flexible substrate 1 or preparing the microneedle array 2 through a microneedle mould, and taking a substrate of the microneedle array 2 as the flexible substrate 1;

step 2, preparing a groove with a pair of slopes 51 on the upper surface of the flexible substrate 1 as a micro-reaction pool 5, or reserving a corresponding groove through a micro-needle mold as the micro-reaction pool 5, wherein the porous structure of the porous micro-needle 21 is communicated with the micro-reaction pool 5 through a micro-channel 23;

step 3, soaking the prepared microneedle array 2 in a glycosaminoglycan solution, and then drying to obtain the microneedle array 2 reinforced by the glycosaminoglycan coating 22;

step 4, performing hydrophilic modification treatment on the flexible substrate 1;

step 5, preparing an LC resonance circuit on the hydrophilic modified flexible substrate 1 by ink-jet printing, wherein two capacitor plates are respectively printed on two opposite slopes 51 of the micro-reaction tank 5;

step 6, injecting gel 52 containing glucolase into the micro-reaction tank 5 as a dielectric material;

and 7, preparing a flexible protective layer 4 for wrapping and protecting the LC resonance circuit on the flexible substrate 1 to finish the preparation of the flexible blood glucose concentration sensor.

As a preferred example, in step 1, the microneedle array 2 is prepared as follows:

(1) Preparing a female die according to the size and distribution of the microneedle array 2 to obtain a microneedle die;

(2) Treating the microneedle mould surface with a surfactant;

(3) Injecting a casting material (such as PDMS doped with citric acid microparticles) doped with water-soluble particles into a mould, and curing for 1 hour at the temperature of 80 ℃ to obtain a microneedle array body;

(3) And soaking the microneedle array body for 48 hours by using deionized water for washing away water-soluble particles and forming capillary pores to obtain the microneedle array 2 with the porous microneedles.

Further preferably, the microneedle mould is a square template with the side length of 13mm, 169 pyramid-shaped needles with the interval of 1mm are arranged on the template, the length of each needle is 1200 μm, and the width of each needle is 620 μm; and placing core moulds in the micro-channel 23 area and the micro-reaction pool 5 area, obtaining the micro-needle array 2 with the micro-channel 23 and the micro-reaction pool 5 after casting molding, and taking the substrate of the micro-needle array 2 as the flexible substrate 1.

It should be noted that the microneedle array preparation process is not limited to the above process, and does not affect the core inventive concept of the present invention, and specifically, the microneedle array 2 may be prepared by referring to the technology disclosed in CN106619480A, in the embodiment of the present invention, and then adhered to the flexible substrate 1 for assembly, or when the microneedle array is cast, the substrate of the microneedle array may be cast a bit thicker to be directly used as the flexible substrate 1, and more preferably, when the microneedle array is cast, a core mold is added to cast and mold the microneedle array 2, the flexible substrate 1, the microchannel 23, and the micro reaction tank 5 at one time.

As a preferred embodiment, in step 2, the micro-reaction tank 5 may be directly formed by casting, or may be formed by post-etching or laser ablation, and is not particularly limited.

In a preferred embodiment, in step 3, the coating material is 20% glycosaminoglycan solution, the material solidifies after being dried for 48 hours at 25 ℃ and 50% humidity, and the porous microneedle 21 has sufficient strength to pierce the surface of the human body by soaking in the glycosaminoglycan solution and drying, so as to collect the tissue fluid.

Further preferably, the glycosaminoglycan is soaked in a common container or in a master mold.

As a preferred embodiment, the specific hydrophilic modification manner in step 4 is to perform oxidation treatment by using an ultraviolet ozone lamp for irradiation, so as to achieve the purpose of hydrophilic modification, thereby facilitating the subsequent inkjet printing.

Specifically, the flexible substrate 1 may be irradiated with an ultraviolet ozone lamp for 2min for oxidation treatment.

As a preferred embodiment, in step 5, the LC resonant circuit is prepared as follows:

printing a second capacitor plate 32 and an outer lead 35 connected with the capacitor plate;

then preparing an insulating layer 34 on the outer lead 35 and exposing the outer end portion of the outer lead 35;

preferably, a spiral coil 33 is printed on the flexible substrate 1 and the insulating layer 34 so as to surround the micro-reaction chamber 5, the inner end of the spiral coil 33 is connected to the first capacitor plate 31 through an inner lead, and the outer end of the spiral coil 33 is connected to the outer end of an outer lead 35.

In a preferred embodiment, the insulating layer 34 is prepared by ink-jet printing or coating, and the solution of the material of the insulating layer 34 is easy to block a nozzle of an ink-jet printing device, so that the coating process commonly used in the semiconductor preparation method can be used instead.

As a preferred embodiment, the LC resonance circuit is prepared by printing the detection circuit 3 with the thickness of 200nm by using nano-silver ink, and then drying the detection circuit 3 at 150 ℃ for 30min to enable the detection circuit 3 to be cured and have the conductivity.

As a preferred embodiment, in step 7, a PDMS film with a thickness of 500nm, i.e. the flexible protection layer 4, is sprayed on the detection circuit 3 by inkjet printing technology.

By changing the glucose concentration in the gel 52 in the micro-reaction cell 5, the resonance frequency of the LC resonance circuit of the measurement sensor is changed at 10% -90% RH, the response curve of the blood glucose concentration of the element is calibrated, and the function of measuring the blood glucose concentration is realized.

The blood glucose concentration sensor in the embodiment is soft and skin-friendly, is convenient to apply for a long time, has a simple structure, low cost, environmental protection and no toxicity, can realize real-time response to the blood glucose concentration with high precision, high sensitivity and high reliability, solves the problem of in-situ continuous monitoring of the blood glucose concentration, mainly adopts an ink-jet printing technology in the preparation method, has the advantages of editable parameters of digital manufacturing, short research and development period, simple process and the like, is suitable for large-scale industrial production, and can be applied to actual scenes of self-checking the blood glucose concentration of a diabetic patient, rapid detection of the blood glucose and the like.

It should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and the present invention is not limited to the above-mentioned embodiments, which are intended to enable those skilled in the art to understand the contents of the present invention and implement the present invention accordingly. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A flexible blood glucose concentration sensor, comprising:

the micro-reaction tank is arranged on the flexible substrate and is used for containing gel containing the glucolase;

the detection circuit is characterized in that two capacitor plates are connected through an inductance coil to form an LC resonance circuit, the two capacitor plates are oppositely arranged in the micro-reaction tank, and gel containing glucolase is used as a dielectric layer;

2. The flexible blood glucose concentration sensor of claim 1, wherein: the micro-reaction tank is at least provided with two opposite slopes, the LC resonance circuit is prepared on the flexible substrate through an ink-jet printing technology, the two capacitor plates are printed on the two slopes, the inductance coil is a spiral coil printed on the flexible substrate around the micro-reaction tank, the inner side end of the spiral coil is directly connected with the first capacitor plate, and the outer side of the spiral coil is isolated through an insulating layer and then connected with the second capacitor plate.

3. The flexible blood glucose concentration sensor of claim 2, wherein: and a flexible protective layer is packaged above the LC resonance circuit of the flexible substrate.

4. The flexible blood glucose concentration sensor of claim 2, wherein: the thickness of the flexible substrate is 0.5-3mm.

5. The flexible blood glucose concentration sensor of claim 2, wherein: the thickness of the LC resonant circuit based on the inkjet printing process is 100-300nm.

6. The flexible blood glucose concentration sensor of claim 2, wherein: the porous microneedle has a tip cone angle of 20-40 degrees and a porosity of 40-70 percent.

7. The flexible blood glucose concentration sensor of claim 2, wherein: the porous microneedle is a flexible porous microneedle, and the surface of the flexible porous microneedle is subjected to strengthening treatment by coating glycosaminoglycan.

8. The flexible blood glucose concentration sensor of claim 2, wherein: the equivalent diameter of the micro-channel is 0.2-1mm.

9. A method of manufacturing a flexible blood glucose concentration sensor according to any one of claims 2-8, comprising the steps of:

step 2, preparing grooves with paired slopes on the upper surface of the flexible substrate as a micro-reaction pool, or reserving corresponding grooves through a micro-needle mold as the micro-reaction pool, wherein the porous structure of the porous micro-needle is communicated with the micro-reaction pool through a micro-channel;

step 4, carrying out hydrophilic modification treatment on the flexible substrate;

10. The method of manufacturing a flexible blood glucose concentration sensor of claim 9, wherein: the LC resonance circuit of step 5 is prepared as follows: