Saliva glucose detection device and method based on hydrogel radio frequency response

Abstract

The invention provides a saliva glucose detection device and method based on hydrogel radio frequency response. The saliva glucose detection device comprises a reader and a glucose detection sensor which are oppositely arranged from top to bottom, wherein the glucose detection sensor comprises glucose sensitive hydrogel and two spiral line couplers arranged on the upper side and the lower side of the glucose sensitive hydrogel in an insulating manner, and wireless coupling is formed between the reader and the spiral line couplers; when the glucose sensitive hydrogel is in contact with glucose molecules to generate thickness response, the distance between the two spiral line couplers is changed, and the resonant frequency of the glucose detection sensor is changed, so that non-invasive detection of glucose in saliva is realized.

Description

Technical Field

[0001] The invention relates to a non-invasive glucose detection method, and in particular to a saliva glucose detection device and method based on hydrogel radio frequency response. Background Art

[0002] With the improvement of living standards and changes in eating habits, diabetes has become a major public health issue worldwide. For diabetic patients, constant monitoring of glucose in the body is the core means to accurately manage the disease, prevent complications, and maintain quality of life.

[0003] Traditional glucose detection methods usually rely on collecting blood samples and analyzing them using electrochemical sensors or spectroscopic instruments. The specific detection method is to implant a tiny probe with enzymes such as glucose oxidase or glucose dehydrogenase under the skin and contact it with the tissue fluid. Based on the correlation between the glucose concentration in the interstitial fluid and the glucose concentration in the blood, the blood glucose level is tested by monitoring the changes in the glucose concentration in the interstitial fluid. The disadvantages are: the probe is made of high-precision processing and is expensive, and the invasion of the probe into the skin will cause pain and psychological pressure to the patient, and increase the risk of infection. In other words, the traditional blood glucose detection method is not only cumbersome to operate, but also brings pain and infection risks to patients. Therefore, it is of great significance to develop a non-invasive and convenient glucose detection method.

[0004] In recent years, saliva glucose detection sensors have gradually attracted attention. Compared with blood, the collection of saliva samples is simpler and non-invasive, and can reflect the changes in glucose levels in the human body. However, existing saliva glucose detection sensors still have some problems:

[0005] 1. Complex manufacturing process: The electrochemical sensor in the current saliva glucose detector usually contains a working electrode, a reference electrode and an auxiliary electrode. When the saliva sample comes into contact with the sensor, glucose undergoes an oxidation reaction on the electrode to generate current. By measuring the magnitude of the current, the concentration of glucose in the saliva can be calculated. The electrodes used in this sensor need to be made by a complex electrochemical process.

[0006] 2. High component cost: The current saliva glucose detector needs to combine wired transmission or Bluetooth transmission to transmit data, resulting in a high cost of the overall saliva glucose detector.

[0007] The above problems of the saliva glucose detection device have greatly limited the wide application of the saliva glucose detection sensor. Summary of the invention

[0008] The purpose of the present invention is to provide a saliva glucose detection device and method based on hydrogel radio frequency response, which detects the glucose content in saliva based on the hydrogel radio frequency response principle and the frequency domain characteristics of wireless radio frequency signals, and provides a solution that can non-invasively, quickly and accurately detect the glucose content in saliva, which not only simplifies the manufacturing process and reduces costs, but also improves the convenience and accuracy of detection.

[0009] To achieve the above objectives, the present technical solution provides a salivary glucose detection device based on hydrogel radio frequency response, comprising:

[0010] A reader and a glucose detection sensor are arranged opposite to each other from top to bottom, wherein the glucose detection sensor includes a glucose-sensitive hydrogel and two spiral couplers insulated and arranged on the upper and lower sides of the glucose-sensitive hydrogel, and a wireless coupling is formed between the reader and the spiral coupler;

[0011] When the glucose-sensitive hydrogel contacts glucose molecules and generates a thickness response, the distance between the two spiral couplers 501 changes, and the resonant frequency of the glucose detection sensor 500 changes.

[0012] The present technical solution provides a method for detecting glucose in saliva based on radio frequency response of hydrogel, characterized in that the detection is performed based on the saliva glucose detection device based on radio frequency response of hydrogel, comprising the following steps: adding the saliva to be tested into the glucose detection sensor; detecting the concentration of glucose in the saliva according to the change in the resonant frequency of the glucose detection sensor;

[0013] Compared with the prior art, this technical solution has the following characteristics and beneficial effects:

[0014] 1. In terms of process flow, the present invention abandons electrochemical processing technology, and constructs glucose-sensitive hydrogel by mixing acrylamide, N,N'-methylenebisacrylamide, 3-acrylamidophenylboric acid, ammonium persulfate, and N,N,N',N'-tetramethylethylenediamine to detect glucose. When the glucose radio frequency sensor contacts saliva, the glucose in the saliva enters the polyacrylamide network (the product of acrylamide polymerization) in the glucose-sensitive hydrogel by diffusion. The glucose in the saliva reacts with the 3-acrylamidophenylboric acid in the polyacrylamide network, thereby increasing the hydrophilicity of the polyacrylamide network. The balance of the original network structure of the glucose-sensitive hydrogel is broken, thereby greatly absorbing the water in the saliva to achieve a new balance. The thickness of the glucose radio frequency sensor is therefore increased, and the resonant frequency changes, thereby achieving sensing detection.

[0015] 2. In terms of component cost, the present invention superimposes a glucose-sensitive hydrogel, an insulating layer and a spiral coupler to form a glucose radio frequency sensor with high sensitivity to saliva, and converts the glucose concentration signal into a coupling state between spiral couplers. The cost of the spiral coupler is much lower than that of the battery.

[0016] 3. In terms of signal reading, the present invention uses an ultra-wideband circular antenna, an ultra-wideband square antenna or an ultra-wideband special-shaped antenna as a reader, and reads the resonant frequency formed by coupling between spiral couplers by wireless radio frequency. The resonant frequency is used to sense the glucose concentration in saliva. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is an exploded view of the salivary glucose detection device based on hydrogel radio frequency response of the present scheme;

[0018] Figure 2 An exploded view of a glucose radio frequency sensor;

[0019] Figure 3 is a top view of the helical coupler;

[0020] Figure 4 Flow chart for formulating glucose-sensitive hydrogel;

[0021] Figure 5 A top view of an inlet layer, a flow channel layer, and a bottom packaging layer used in a salivary glucose detection device;

[0022] Figure 6 is a calibration curve diagram of the resonance frequency between the helical couplers versus glucose concentration;

[0023] Figure 7 is a linear correlation diagram between the salivary glucose detection method and the glucose oxidase detection method;

[0024] Figure 8 The trend of saliva and blood glucose concentration during glucose tolerance test;

[0025] Fig. 9 The trend of changes in saliva and blood glucose concentrations during a high-carbohydrate diet;

[0026] Fig.10The trend of saliva and blood glucose concentration changes during a low-carb diet. In the figure: 100, reader, 200, inlet layer, 201, sensor placement area, 202, saliva inlet, 203, assembly hole, 300, flow channel layer, 301, flow channel, 302, assembly column, 400, bottom packaging layer, 500, glucose RF sensor, 501, sensor packaging layer, 502, first insulating layer, 503, glucose sensitive hydrogel, 504, second insulating layer, 505, first spiral coupler, 506, second spiral coupler. DETAILED DESCRIPTION

[0027] The following will be combined with the accompanying drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0028] Those skilled in the art should understand that, in the disclosure of the present invention, the orientation or position relationship indicated by the terms "longitudinal", "lateral", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc. are based on the orientation or position relationship shown in the drawings, which are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operate in a specific orientation. Therefore, the above terms should not be understood as limiting the present invention.

[0029] Embodiment 1

[0030] Figure 1 Schematic diagram of the structure of the saliva glucose detection device based on hydrogel radio frequency response provided by this scheme, such as Figure 1 As shown, the saliva glucose detection device based on hydrogel radio frequency response includes:

[0031] A reader 100 and a glucose detection sensor 500 are arranged opposite to each other from top to bottom, wherein the glucose detection sensor includes a glucose sensitive hydrogel 503 and two spiral couplers insulated and arranged on the upper and lower sides of the glucose sensitive hydrogel 503, and a wireless coupling is formed between the reader 100 and the spiral coupler;

[0032] When the glucose-sensitive hydrogel 503 contacts glucose molecules and generates a thickness response, the distance between the two spiral couplers 501 changes, and the resonant frequency of the glucose detection sensor 500 changes.

[0033] This scheme uses the hydrogel radio frequency response principle that the glucose-sensitive hydrogel 503 generates a thickness response after absorbing glucose in saliva to realize glucose detection in saliva. When the glucose-sensitive hydrogel 503 absorbs glucose molecules in saliva, the hydrophilicity of the internal cross-linked network of the glucose-sensitive hydrogel 503 is enhanced, which in turn causes the glucose-sensitive hydrogel 503 to absorb more water, thereby increasing the thickness of the glucose-sensitive hydrogel 503, and thus causing the distance between the two spiral couplers to increase, thereby changing the resonant frequency of the glucose detection sensor 500. Through calibration, the magnitude of the change in the resonant frequency signal of the glucose detection sensor 500 uniquely corresponds to the concentration of glucose in the liquid it contacts, so the glucose radio frequency sensor sensing the glucose concentration detection can be realized by using the change in the resonant frequency of the glucose detection sensor 500.

[0034] like Figure 2 As shown, the glucose detection sensor 500 includes a sensing packaging layer 501, a first insulating layer 502, a glucose sensitive hydrogel 503 and a second insulating layer 504 which are arranged in sequence from top to bottom, wherein the first spiral coupler 505 is arranged on the upper surface of the first insulating layer 502, the second spiral coupler 506 is arranged on the lower surface of the second insulating layer 504, and the glucose sensitive hydrogel 503 is adhered to the upper surfaces of the first insulating layer 502 and the second insulating layer 504, so that when the thickness of the glucose sensitive hydrogel 503 changes, the distance between the first spiral coupler 505 and the second spiral coupler 506 changes accordingly, thereby changing the resonant frequency of the glucose detection sensor 500.

[0035] Specifically, the sensing packaging layer 501 is provided with a hole array to facilitate glucose molecules to enter the glucose RF sensor 500 and contact the glucose sensitive hydrogel 503. In some embodiments, the holes on the sensing packaging layer 501 are prepared by laser cutting to make it easier for glucose molecules in saliva to enter the glucose sensitive hydrogel 503.

[0036] It should be noted that saliva and glucose are in direct contact with the glucose-sensitive hydrogel 503, but in order to allow more areas of the glucose-sensitive hydrogel 503 to contact the glucose in the saliva, holes are opened on the encapsulation layer 501 so that the bottom area of ​​the glucose-sensitive hydrogel 503 can also react with the glucose in the saliva. In this way, the reaction is more complete and the overall sensing detection time is also shorter.

[0037] Preferably, the holes in the sensing packaging layer 501 are provided with a selective film that only allows glucose molecules to pass through.

[0038] It should be emphasized that the glucose detection sensor 500 of the present solution forms a structure of "first spiral coupler 505 - glucose sensitive hydrogel 503 - second spiral coupler 506" which can "both form a built-in capacitor and generate an electromagnetic signal".

[0039] Furthermore, a first insulating layer 502 is arranged between the glucose-sensitive hydrogel 503 and the first spiral coupler 505, and a second insulating layer 504 is arranged between the glucose-sensitive hydrogel 503 and the second spiral coupler 506. The insulating layer is arranged to provide electrical insulation to prevent moisture inside the glucose-sensitive hydrogel 503 from interfering with the radio frequency signal between the first spiral coupler 505 and the second spiral coupler 506.

[0040] like Figure 4 As shown, the preparation method of glucose sensitive hydrogel 503 is as follows:

[0041] A hydrogel pre-solution was prepared by adding acrylamide and N,N'-methylenebisacrylamide into deionized water;

[0042] The glucose-sensitive hydrogel was synthesized by mixing the hydrogel pre-solution, 3-acrylamidophenylboronic acid dissolved in ethanol, ammonium persulfate and N,N,N',N'-tetramethylethylenediamine in a centrifuge tube.

[0043] It should be noted that the glucose-sensitive hydrogel 503 of the present embodiment contains 3-acrylamidophenylboronic acid. After 3-acrylamidophenylboronic acid reacts with glucose in saliva, the hydrophilicity is enhanced, so that the hydrogel absorbs more water and becomes thicker, thereby realizing sensing detection.

[0044] In a specific embodiment, acrylamide (mass fraction 20%) and N,N'-methylenebisacrylamide (mass fraction 1%) are added to deionized water to prepare a hydrogel pre-solution, and 80 μL of the hydrogel pre-solution, 90 μL of 0.32 mol / L 3-acrylamidophenylboronic acid (dissolved in 53.85% ethanol), 5 μL of 2 mol / L ammonium persulfate and 3 μL of 0.8 mol / L N,N,N',N'-tetramethylethylenediamine are mixed in a centrifuge tube and allowed to stand for 10 minutes to synthesize a glucose-sensitive hydrogel.

[0045] In some embodiments, the first spiral coupler 505 and the second spiral coupler 506 have the same shape or different shapes, and the shape of the first spiral coupler 505 and the second spiral coupler 506 is selected from one of a square spiral, a circular spiral, and a polygonal spiral.

[0046] like Figure 3As shown, in a specific embodiment of the present solution, the first spiral coupler 505 and the second spiral coupler 506 are designed as square spirals.

[0047] In some embodiments, the first spiral coupler 505 and the second spiral coupler 506 are manufactured by wet etching or screen printing.

[0048] In addition, in some embodiments, the insulating material of the first insulating layer 502 and the second insulating layer 504 is a polyethylene terephthalate film or a polyimide film.

[0049] In some embodiments, the reader 100 is used to generate and receive wireless radio frequency signals, and the inductor coil is made by wet etching or screen printing technology. The manufacturing method is as follows: first, a suitable substrate is selected as a carrier of the inductor coil. The substrate should have good conductivity and stability, and then a pattern of the inductor coil is made on the substrate by photolithography or printing technology.

[0050] Preferably, the shape and size of the antenna pattern used in the reader can be adjusted according to actual needs. The antenna is etched or printed on the substrate using wet etching or screen printing technology. During the etching or printing process, the lines of the antenna should be clear and uniform. The inductor coil obtained by etching or printing is processed to improve its conductivity and stability. The processing method may include steps such as cleaning and drying. During the manufacture of the antenna, its shape and size can be adjusted according to actual needs. The manufactured antenna should have good conductivity and stability to ensure the transmission effect of the wireless radio frequency signal. In some embodiments, the reader 100 is an ultra-wideband circular antenna, an ultra-wideband square antenna, or an ultra-wideband special-shaped antenna.

[0051] In addition, in some embodiments, the saliva glucose detection device also includes a data analysis terminal (not shown in the figure). In some embodiments, the data analysis terminal uses a vector network analyzer to receive the wireless radio frequency signal transmitted by the inductive coil of the reader 100 and convert it into a readable glucose concentration value. The selection of the vector network analyzer should be considered according to actual needs to ensure the reading range and accuracy of the signal.

[0052] In some embodiments, the reader 100 and the glucose detection sensor 500 of the saliva glucose detection device based on hydrogel radio frequency response are arranged on a structure, which includes the reader 100, the inlet layer 200, the flow channel layer 300 and the bottom packaging layer 400 arranged in sequence from top to bottom, wherein the inlet layer 200 is provided with a saliva inlet 202, and the glucose detection sensor 500 is arranged on the flow channel layer 300 and communicated with the saliva inlet 201.

[0053] The flow channel layer 300 is provided with a flow channel 301, one end of the flow channel 301 is communicated with the saliva inlet 202, and the glucose detection sensor 500 is arranged at the other end of the flow channel 301. Specifically, the glucose sensitive hydrogel 503 is arranged at the other end of the flow channel layer 300 and communicated with the saliva inlet 202, that is, the saliva enters the flow channel layer 300 from the saliva inlet 202, enters the glucose sensitive hydrogel 503 along the flow channel 301, and reacts.

[0054] Specifically, Figure 5 As shown, a saliva inlet 202 and a sensor placement area 201 are spaced apart on the inlet layer 200 , one end of the flow channel 301 is arranged opposite to the saliva inlet 202 , and the other end is arranged opposite to the sensor placement area 201 , and the glucose detection sensor 500 is arranged in the sensor placement area 201 and one end of the flow channel 301 .

[0055] When the collected saliva drips in from the inlet 202, it enters the reaction pool 301 along the flow channel 301 and contacts the glucose RF sensor 500 in the sensor placement area 201, thereby changing the resonant frequency emitted by the glucose RF sensor 500, and wireless coupling occurs between the RF signal emitted by the reader 100 and the sensor, thereby detecting the glucose concentration in the saliva.

[0056] In some embodiments, the saliva glucose detection device additionally includes a saliva collector (not shown), which is arranged relative to the saliva inlet 202. Preferably, the upper end of the saliva collector is a circular port, and the lower end is embedded in a base for transporting saliva to the flow channel 301.

[0057] This scheme provides a method for detecting glucose in saliva based on hydrogel radio frequency response, comprising:

[0058] Adding the saliva to be tested into the glucose detection sensor 500;

[0059] The concentration of glucose in saliva is detected based on the amount of change in the resonance frequency of the glucose detection sensor 500 .

[0060] Specifically, the change in the resonant frequency of the glucose detection sensor 500 can be substituted into the frequency shift rate-glucose concentration linear equation to obtain the concentration of glucose in saliva. The frequency shift rate-glucose concentration linear equation for a specific saliva glucose detection device based on hydrogel radio frequency response is as follows: Figure 6 As shown, it can be seen that the change in resonant frequency is linearly related to the glucose concentration.

[0061] In addition, 16 samples of saliva were collected from the subjects, and their glucose concentrations were detected using the glucose oxidase method and the radio frequency sensing method of this project, respectively. The linear correlation between the two was compared to obtain the linear correlation between the saliva glucose detection method based on the hydrogel radio frequency response and the glucose oxidase detection method. Figure 7 shown.

[0062] Using the technical method of this project and the commercial Abbott Freestyle Libre 2Plus instant blood glucose meter, the concentration changes of blood sugar and salivary glucose of the same subject undergoing glucose tolerance test were tested between 09:30 and 13:30. The specific process of the glucose tolerance test is that the subject fasted for 14 hours before the test and took 75g of edible anhydrous glucose every 30 minutes starting from 09:30. The actual test results obtained for the glucose tolerance test example are as follows: Figure 8 As shown, it can be seen that when blood sugar rises sharply, the saliva glucose detection device based on hydrogel radio frequency response can sense its changing trend.

[0063] Using the technical methods of this project and the commercial Abbott Freestyle Libre 2Plus instant blood glucose meter, the changes in blood glucose and salivary glucose concentrations of the same subject who was undergoing a high-carb test were tested between 14:00 and 18:00. The specific process of the high-carb test is that the subject starts to consume high-carb foods such as hamburgers and cola at 14:00, and the actual test results for the high-carb food example test are as follows: Fig. 9 As shown, when blood sugar increases slightly, the saliva glucose detection device based on hydrogel radio frequency response can sense its changing trend.

[0064] Using the technical method of this project and the commercial Abbott Freestyle Libre 2Plus instant blood glucose meter, the concentration changes of blood glucose and salivary glucose of the same subject who was undergoing the low-carb test were tested between 18:30 and 21:30. The specific process of the low-carb test is that the subject starts to consume low-carb foods such as broccoli and cucumber at 18:30. The actual test results for the low-carb food example test are as follows: Fig.10 As shown, it can be seen that when blood sugar rises slightly, the saliva glucose detection device based on hydrogel radio frequency response can sense its changing trend.

[0065] Those skilled in the art should understand that the technical features of the above embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0066] The above embodiments only express several implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the present application. It should be pointed out that, for a person of ordinary skill in the art, several variations and improvements can be made without departing from the concept of the present application, and these all belong to the protection scope of the present application. Therefore, the protection scope of the present application shall be subject to the attached claims.

Claims

1. A saliva glucose detection device based on hydrogel radio frequency response, characterized in that: include: A reader and a glucose detection sensor are arranged opposite to each other from top to bottom, wherein the glucose detection sensor includes a glucose-sensitive hydrogel and two spiral couplers insulated and arranged on the upper and lower sides of the glucose-sensitive hydrogel, and a wireless coupling is formed between the reader and the spiral coupler; When the glucose-sensitive hydrogel contacts glucose molecules and responds to its thickness, the spacing between the two helical couplers changes and the resonant frequency of the glucose detection sensor changes.

2. The saliva glucose detection device based on hydrogel radio frequency response according to claim 1, characterized in that: The glucose detection sensor includes a sensor packaging layer, a first insulating layer, a glucose-sensitive hydrogel and a second insulating layer which are arranged in sequence from top to bottom, wherein the first spiral coupler is arranged on the upper surface of the first insulating layer, the second spiral coupler is arranged on the lower surface of the second insulating layer, and the glucose-sensitive hydrogel is adhered to the upper surfaces of the first insulating layer and the second insulating layer.

3. The saliva glucose detection device based on hydrogel radio frequency response according to claim 1, characterized in that: At least one hole is formed on the sensor packaging layer.

4. The saliva glucose detection device based on hydrogel radio frequency response according to claim 1, characterized in that: The preparation method of glucose-sensitive hydrogel is as follows: acrylamide and N,N'-methylenebisacrylamide are added to deionized water to prepare a hydrogel pre-solution; the hydrogel pre-solution, 3-acrylamidophenylboronic acid dissolved in ethanol, ammonium persulfate and N,N,N',N'-tetramethylethylenediamine are mixed in a centrifuge tube to synthesize the glucose-sensitive hydrogel.

5. The saliva glucose detection device based on hydrogel radio frequency response according to claim 1, characterized in that: The first spiral coupler and the second spiral coupler 506 have the same shape or different shapes. The shape of the first spiral coupler and the second spiral coupler 506 is selected from one of a square spiral, a circular spiral, and a polygonal spiral.

6. The saliva glucose detection device based on hydrogel radio frequency response according to claim 1, characterized in that: The insulating material of the first insulating layer and the second insulating layer is a polyethylene terephthalate film or a polyimide film.

7. The saliva glucose detection device based on hydrogel radio frequency response according to claim 1, characterized in that: The reader and the glucose detection sensor are arranged on a structure, which includes a reader, an inlet layer, a flow channel layer and a bottom packaging layer arranged in sequence from top to bottom, wherein a saliva inlet is arranged on the inlet layer, and the glucose detection sensor is arranged on the flow channel layer and communicated with the saliva inlet.

8. The saliva glucose detection device based on hydrogel radio frequency response according to claim 7, characterized in that: A flow channel is arranged on the flow channel layer, one end of the flow channel is communicated with the saliva inlet, and the glucose sensitive hydrogel is arranged on the other end of the flow channel layer and is communicated with the saliva inlet.

9. The saliva glucose detection device based on hydrogel radio frequency response according to claim 7, characterized in that: A saliva inlet and a sensor placement area are provided on the inlet layer, one end of the flow channel is arranged opposite to the saliva inlet, and the other end is arranged opposite to the sensor placement area. The glucose detection sensor is arranged in the sensor placement area and one end of the flow channel.

10. A method for detecting saliva glucose based on hydrogel radio frequency response, characterized in that: The detection is performed based on the saliva glucose detection device based on hydrogel radio frequency response according to any one of claims 1 to 9, comprising the following steps: Adding the saliva to be tested into the glucose detection sensor; The concentration of glucose in saliva is detected based on the amount of change in the resonance frequency of the glucose detection sensor.

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