Tear self-powered blood glucose monitoring contact lens

Abstract

The invention provides tear self-powered blood glucose monitoring contact lenses, and belongs to the technical field of biomedical monitoring. The contact lens provided by the invention can generate power by using tears of human eyes, namely, generate power by converting latent heat energy released by water vapor in a condensation process, can stably supply power to a system after reasonable series connection, and has good biocompatibility. In the application process of the self-powered blood glucose monitoring type contact lens based on the chitosan water power generation bio-compatible material provided by the invention, the adopted chitosan has good biocompatibility; the water photovoltaic power generation device can utilize abundant atmospheric water vapor, output of electric energy is achieved by converting latent heat energy released by the water vapor in the condensation process, and no heating problem is caused. The glucose concentration sensor can accurately measure the current response on the working electrode by using a three-electrode system.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical monitoring, and in particular to a tear self-powered blood sugar monitoring contact lens. Background Art

[0002] Contact lenses are widely used in vision correction as a universal technology. With the development of the Internet of Things, electronic technology, micro-nano processing technology, materials and sensor technology, smart contact lenses with diagnostic functions are developing rapidly. Contact lenses are in continuous contact with the eyes, which provides a unique platform for continuous monitoring of tear glucose levels, lactate levels, intraocular pressure, eye tracking and drug release. The human eye is constantly infiltrated by tears, which contain many chemical analytes, such as glucose, lactate, immunoglobulins, etc., among which glucose concentration can be used to continuously monitor related diseases such as diabetes.

[0003] At present, the commonly used blood glucose monitoring mainly adopts invasive methods, which collects blood by needles to achieve single monitoring. Several tests require several blood draws, which have the disadvantages of easy infection and inaccurate and discontinuous detection. The current wearable tear blood glucose monitoring technology often uses external chemical fuel cells for power supply or induction coils to wirelessly receive energy, which has the defects of low integration and heat generation. In addition, the electrochemical sensor used to detect the concentration of glucose in tears is large in size, not sensitive enough, and difficult to prepare. In this context, the use of clean energy to develop wearable equipment has attracted much attention. However, in the existing clean energy power supply technology, the biosafety of functional layer materials (such as graphene oxide) has not been verified, and the output current of the power generation device is small and the load capacity is poor. In addition, the manufacture of hydrovoltaic power generation devices requires pretreatment of materials, such as plasma oxidation, chemical oxidation, and electric field induction, to meet the requirements of different concentration gradient distributions, and the manufacturing process is relatively complicated. In addition, the manufactured device is relatively fragile and lacks flexibility. These factors limit the practical application of hydrovoltaic power generation devices.

[0004] Chinese patent CN116019447A discloses a contact lens-type tear glucose sensor monitoring system, which uses an external circuit to transmit data, an electrochemical sensor is set on the contact lens, and a graphene-based sensor is also used. Its biosafety has not yet been verified.

[0005] Chinese patent CN112603258A discloses an intraocular pressure monitoring smart contact lens, which is powered by external radio frequency (RF) power supply. The wireless power supply distance is limited and has the defect of generating heat, and the safety for human eyes cannot be guaranteed. Summary of the invention

[0006] The purpose of the present invention is to provide a tear self-powered blood glucose monitoring contact lens, which can use the tear moisture of the human eye to generate electricity, that is, to generate electricity by converting the latent heat energy released by water vapor during the condensation process, and after reasonable series connection, the system can be stably powered and has good biocompatibility.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] The present invention provides a tear self-powered blood glucose monitoring contact lens, comprising a substrate, a hydrovoltaic power generation device, an energy management module, a blood glucose monitoring module, a transimpedance amplifier circuit and a Bluetooth module;

[0009] Wherein, the hydrovoltaic generator device comprises: a substrate, an electrode and a chitosan-organic acid-potassium chloride functional layer.

[0010] Preferably, the chitosan-organic acid-potassium chloride functional layer is prepared by a preparation method comprising the following steps:

[0011] Mixing a chitosan organic acid hydrogel dispersion and a potassium chloride solution to obtain a functional layer dispersion;

[0012] The functional layer dispersion is deposited on the electrode and dried to obtain the chitosan-organic acid-potassium chloride functional layer.

[0013] Preferably, the concentration of the chitosan organic acid hydrogel dispersion is 10 to 30 mg / mL;

[0014] The concentration of the potassium chloride solution is 250-350 mg / mL.

[0015] Preferably, the solvent used in the chitosan organic acid hydrogel dispersion is a weak acid solution.

[0016] Preferably, the weak acid solution is a citric acid solution;

[0017] The concentration of the citric acid solution is 50-150 mg / ml.

[0018] Preferably, the chitosan organic acid hydrogel dispersion and the potassium chloride solution are independently subjected to magnetic stirring before mixing;

[0019] The rotation speed of the magnetic stirring is 300-500 rpm.

[0020] Preferably, the total mixing time is 60 to 120 minutes.

[0021] Preferably, the substrate provides the optical function of a contact lens;

[0022] The hydrovoltaic power generation devices can output a voltage large enough to supply the Bluetooth chip and the transimpedance amplifier circuit with work after being connected in series;

[0023] The blood sugar detection module is composed of a three-electrode system, which converts the blood sugar concentration into a current signal, which is then converted into a voltage signal through a transimpedance amplifier circuit and output to the Bluetooth module;

[0024] The energy management module is used to increase the current and assist in completing the information transmission;

[0025] The hydrovoltaic power generation device is arranged at the bottom of the circuit.

[0026] Preferably, the circuit in the contact lens is arranged on the substrate in a fan-shaped shape, and the conical geometry of the contact lens is formed by merging the busbars at both ends of the fan-shaped.

[0027] The curvature and taper of the contact lens are adjusted by changing the geometry of the adjustment sector and the position of the generatrix.

[0028] Preferably, the three-electrode system in the blood glucose detection module includes a working electrode, a reference electrode and a counter electrode;

[0029] The working electrode and the counter electrode form a current loop, and the counter electrode plays a role in current conduction;

[0030] The working electrode and the reference electrode form a voltage loop, the reference electrode serves as a reference for measuring or applying the potential of the working electrode, and the potential of the working electrode is the potential relative to the reference electrode;

[0031] The surface of the working electrode is coated with glucose oxidase;

[0032] Preferably, the material of the working electrode is platinum;

[0033] The material of the reference electrode is silver;

[0034] The material of the counter electrode is carbon.

[0035] Beneficial effects of the present invention:

[0036] In the application process of the self-powered blood glucose monitoring contact lens based on chitosan hydrovoltaic biocompatible material provided by the present invention, as for the power supply mode: chitosan has good biocompatibility; the hydrovoltaic power generation device utilizes abundant atmospheric water vapor to realize the output of electric energy by converting the latent heat energy released by the water vapor during the condensation process, and will not cause any heating problem; as for the glucose concentration sensor: using a three-electrode system, the current response on the working electrode can be accurately measured, and the preparation is relatively simple.

[0037] The self-powered blood glucose monitoring contact lens preparation method provided by the present invention has the following advantages:

[0038] (1) Chitosan-organic acid has abundant hydroxyl groups and excellent adhesion, which can not only absorb water molecules, but also improve the adhesion between the functional layer film and the substrate material, thereby improving the working stability and electrical performance of the device. The abundant hydrophilic groups and large specific surface area in the chitosan / organic acid / potassium chloride functional film layer after the optimized ratio jointly improve the water absorption performance.

[0039] (2) The circuit in the contact lens is arranged on the substrate in the shape of a fan, and the conical geometry of the contact lens is formed by merging the busbars at both ends of the fan; the curvature and taper of the contact lens can be adjusted by changing the geometric shape of the fan and the position of the busbar.

[0040] (3) The electrode was prepared by blade pressure coating, which effectively reduced the contact internal resistance between the electrode and the humidity-sensitive functional layer and provided an unimpeded diffusion channel for the proton dissociation of the carboxyl and amino functional groups of the chitosan / organic acid / potassium chloride functional film layer, greatly increasing the output current of the device and improving product performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is a functional block diagram of contact lenses;

[0042] Figure 2 The schematic diagram of the contact lens circuit, where (A) is the top-level circuit layout (integrating the Bluetooth module, energy management module, and spanning amplifier circuit); (B) is the bottom-level circuit layout (integrating the hydrovoltaic power generation module and the electrochemical sensor); (C) is the electrochemical sensor of the three-electrode system; (D) is the circuit closure diagram along the busbar;

[0043] Figure 3 This is a diagram of the composition of a hydrovoltaic power generation device;

[0044] Figure 4 The present invention is a process flow chart for preparing the functional layer of a hydrovoltaic power generation device;

[0045] Figure 5 The diagram shows the composition of the hydrovoltaic generator unit module, where (A) is a physical picture of a contact lens (7 power generation unit modules are connected in series); (B) is the microstructure of the functional layer of the chitosan / citric acid / potassium chloride composite material; (C) is the output voltage of 7 power generation units connected in series; (D) is the output current of 7 power generation units connected in series;

[0046] Figure 6 This is a diagram of the series and parallel power control of hydroelectric generator devices;

[0047] Figure 7 Schematic diagram of a three-electrode system, where (A) is a schematic diagram of a glucose sensor with a three-electrode system; (B) is a diagram showing the relationship between current magnitude and glucose concentration. DETAILED DESCRIPTION

[0048] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0049] Example

[0050] This embodiment provides a new type of hydrovoltaic power generation contact lens for blood glucose detection based on a chitosan / citric acid / potassium chloride composite material. The functional block diagram is as follows: Figure 1 shown.

[0051] The contact lens is mainly composed of a substrate, a hydrovoltaic power generation device, an energy management module, a blood sugar monitoring module, a transimpedance amplifier circuit and a Bluetooth module. The substrate mainly provides the optical function of the contact lens; the hydrovoltaic power generation device can output a sufficiently large voltage for the Bluetooth chip and the transimpedance amplifier circuit to work after being connected in series; the blood sugar detection module is composed of a self-made three-electrode system, which can convert the blood sugar concentration into a current signal, and then convert it into a voltage signal through the transimpedance amplifier circuit and output it to the Bluetooth module. Since the Bluetooth module requires a large working power, the energy management module is used to increase the current and complete the information transmission.

[0052] The contact lens is powered by hydrovoltaic power generation based on chitosan / citric acid / potassium chloride. It can generate electricity by using the water content of tears in the human eye, that is, by converting the latent heat energy released by water vapor during the condensation process to generate electricity, and after reasonable series connection, it can stably power the system and has good biocompatibility. In addition, the contact lens has a highly sensitive three-electrode system glucose sensor. By using the working electrode to coat glucose oxidase, the reference electrode as a reference for measuring or applying the working electrode potential, and the electrode to conduct the current, a highly sensitive and easy-to-prepare electrochemical sensor function for converting glucose concentration into a current signal can be realized.

[0053] The substrate is made of flexible transparent material. In order to ensure the wearability and economy of the contact lenses, a fan-shaped circuit is used and PI reinforcement is used to prevent the chip from detaching. Figure 2 The advantage of using a fan-shaped circuit is that the substrate can be combined along the busbar and fixed with bio-gel to obtain a curvature shape that is suitable for human eyes, which greatly reduces the production cost and is easy to change the size.

[0054] Circuit Layout diagram Figure 2 A. Figure 2As shown in Figure B. The hydrovoltaic power generation device is placed at the bottom of the circuit, and after being coated with a chitosan / citric acid / potassium chloride functional film layer electrode, it is used as the negative electrode, and copper foil and biogel are connected to the pad (as the positive electrode) to power the circuit. Since the Bluetooth module requires high power to transmit information, and the voltage provided by hydrovoltaic power generation is large and the current is small, the power requirement of the Bluetooth module cannot be met, so an energy management module is used to store and release energy.

[0055] like Figure 2 C shows an electrochemical sensor, which is a three-electrode system consisting of a working electrode, a reference electrode, and a counter electrode. The working electrode is coated with glucose oxidase, which can decompose glucose in a glucose solution and generate currents of different magnitudes according to the concentration; the reference electrode not only provides a stable reference potential to control the potential of the working electrode, but also participates in the current loop; at the same time, the counter electrode allows the current to flow through the counter electrode instead of the reference electrode, thereby ensuring the stability of the potential of the reference electrode.

[0056] Since the glucose sensor outputs a current signal and the Bluetooth chip can only collect voltage signals, a transimpedance amplifier circuit is required to convert the current signal into a voltage signal and then transmit it to the Bluetooth chip, and then wirelessly transmit it to an external device via the Bluetooth chip.

[0057] The components of hydrovoltaic power generation devices are as follows: Figure 3 As shown, the hydrovoltaic generator device includes: 1) a PI flexible substrate, 2) an electrode and 3) a chitosan / potassium chloride citrate functional layer.

[0058] The preparation process of chitosan-citric acid dispersion (CS / CA) and potassium chloride (KCl) functional layer is as follows Figure 3 As shown:

[0059] 1) Preparation of citric acid solution. When preparing the citric acid solution, 3 g of citric acid crystals were added to 20 mL of deionized water. Then, the mixture was heated and stirred at a magnetic stirring speed of 400 rpm and a temperature of 50°C. Subsequently, additional deionized water was added to bring the total volume to 30 mL. This resulted in a citric acid solution with a concentration of 100 mg / mL. During this stirring process, the mixture was sealed with a film to prevent evaporation or contamination, and the procedure lasted for about 90 minutes.

[0060] 2) Pretreatment of CS dispersion. A CS dispersion with a concentration of 10 mg / mL was used. In the pretreatment, CS powder was dissolved in citric acid with a concentration of 100 mg / ml so that the mass ratio of CS to CA was 1:10, and stirred at a speed of 400 rpm for 1 hour. During this stirring process, the mixture was sealed with a film to prevent evaporation or contamination, and finally a chitosan hydrogel dispersion was obtained.

[0061] 3) Preparation of KCl solution: The KCl concentration was set to 300 mg / ml, the maximum solubility at room temperature, and the stirring speed was 400 rpm, controlled by a magnetic stirrer.

[0062] 4) Preparation of CS / CA / KCl mixture. To prepare the CS / CA / KCl mixture, a certain amount of KCl solution was dropped into the pretreated chitosan dispersion with a concentration of 10 mg / mL, so that the final mass ratio of CS to citric acid to KCl was 1:10:5. The operation was carried out at room temperature, the stirring speed was 400 rpm, and the stirring was controlled by a magnetic stirrer. To ensure the consistency and purity of the stirring process, the beaker was sealed with a film and the stirring was continued for 90 minutes. The functional layer material was obtained.

[0063] Preparation process of a single module of a hydroelectric generator device:

[0064] The hydrovoltaic generator device is composed of a flexible PI (Polyimide) substrate, a CS / CA / KCl functional layer and a pair of electrodes, which in this embodiment are a gold-plated electrode and an aluminum (Al) electrode.

[0065] 1) The PI film washed with deionized water is used as the substrate of the moisture generator;

[0066] 2) After drying, the functional layer material prepared in the above steps is uniformly deposited on the Au bottom electrode by spin coating, and then dried at 80° C. for 1 h to obtain a CS / CA / KCl functional layer.

[0067] 3) Finally, an aluminum mesh electrode is placed on the CS / CS / KCl functional layer, such as Figure 4 shown.

[0068] Figure 5 (C) (D) are the test and characterization results of the hydrovoltaic generator unit module. Under 80% relative humidity conditions, 7 series-connected hydrovoltaic generator modules can output an open circuit voltage of 3.2V ( Figure 5 C), and a peak current of 43μA ( Figure 5 D). The composite material presents a crisscross pore structure that contributes to the strong capillary action of the material, improves water absorption and enhances the response speed to water ( Figure 5 B), while significantly increasing the number of atoms exposed at the edge and the space for active adsorption of water molecules, thereby improving energy conversion efficiency. The hydrovoltaic generator system can be modularly expanded according to design requirements.

[0069] The functional units of the hydropower generator device have a simple structure and clear hierarchy, which makes them easy to integrate and expand. Figure 6The test results of the series voltage regulation of the hydroelectric generator device are as follows: through the series integration example of 1 to 5 generator unit modules, a linear and controllable increase in output voltage can be achieved. The number of series units can be adjusted according to the power requirements of the external circuit (not limited to 5), which can provide flexible voltage standards and expand the application range of the hydroelectric generator device.

[0070] Figure 7 Shown are (A) schematic diagram of a glucose sensor with a three-electrode system and (B) the relationship between current magnitude and glucose concentration;

[0071] Preparation of three-electrode system glucose sensor, measurement of relevant data and function fitting:

[0072] The three electrodes are: working electrode (WE), reference electrode (RE), and counter electrode (CE), which constitute two loops: a current loop and a voltage loop. The working electrode and the counter electrode constitute a current loop, and the counter electrode plays a role in current conduction. The working electrode and the reference electrode constitute a voltage loop, and the reference electrode is used as a reference for measuring or applying the potential of the working electrode. The potential of the working electrode is also the potential relative to the reference electrode. The working electrode is the place for electrochemical reactions, and the electrochemical reactions occur on its surface. The present invention coats glucose oxidase thereon. Since the reference electrode does not participate in the flow of large currents, its potential can be kept stable, thereby achieving precise control of the potential of the working electrode. The current between the working electrode and the auxiliary electrode is not affected by changes in the potential of the reference electrode, and the current response on the working electrode can be accurately measured. The auxiliary electrode bears most of the current to prevent the reference electrode from polarizing due to excessive current, thereby ensuring the reliability of the potential reference.

[0073] Platinum is selected as the material of the working electrode, which has the characteristics of chemical inertness, electrochemical stability, excellent conductivity, modifiability, etc., and meets the requirements of the working electrode. Silver is selected as the material of the reference electrode, which has good chemical stability and can ensure the accuracy of electrochemical measurement. Carbon is selected as the material of the counter electrode, which has excellent conductivity, can effectively transfer charge, and promote the electrochemical reaction.

[0074] BSA (10 mg / ml) and GOx (50 mg / ml) were dissolved in a 2% mass fraction PVA solution to form a mixed solution, which was then mixed with a 0.5%wt chitosan solution (solvent: 1 mol / L acetic acid solution) at a ratio of 1:1 to obtain a glucose oxidase mixed solution. Next, the glucose oxidase was fixed at the working electrode.

[0075] The electrochemical sensor of the three-electrode system was tested using an electrochemical workstation CHI760E, and the fitting function of different currents corresponding to different glucose concentrations was obtained. Figure 7As can be seen in (b), the current I increases with the increase of glucose concentration C, and their changing trends are close to the following fitting formula:

[0076] I=0.6291×C+1.438

[0077] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A tear self-powered blood glucose monitoring contact lens, characterized in that: It includes a substrate, a hydrovoltaic power generation device, an energy management module, a blood sugar monitoring module, a transimpedance amplifier circuit and a Bluetooth module; Wherein, the hydrovoltaic generator device comprises: a substrate, an electrode and a chitosan-organic acid-potassium chloride functional layer.

2. The tear self-powered blood glucose monitoring contact lens according to claim 1, characterized in that: The chitosan-organic acid-potassium chloride functional layer is prepared by a preparation method comprising the following steps: Mixing a chitosan organic acid hydrogel dispersion and a potassium chloride solution to obtain a functional layer dispersion; The functional layer dispersion is deposited on the electrode and dried to obtain the chitosan-organic acid-potassium chloride functional layer.

3. The tear self-powered blood glucose monitoring contact lens according to claim 2, characterized in that: The concentration of the chitosan organic acid hydrogel dispersion is 10 to 30 mg / mL; The concentration of the potassium chloride solution is 250-350 mg / mL.

4. The tear self-powered blood glucose monitoring contact lens according to claim 3, characterized in that: The solvent used in the chitosan organic acid hydrogel dispersion is an organic weak acid solution.

5. The tear self-powered blood glucose monitoring contact lens according to claim 4, characterized in that: The organic weak acid solution is a citric acid solution; The concentration of the citric acid solution is 50-150 mg / ml.

6. The tear self-powered blood glucose monitoring contact lens according to claim 2, characterized in that: The chitosan organic acid hydrogel dispersion and the potassium chloride solution are independently subjected to magnetic stirring before mixing; The rotation speed of the magnetic stirring is 300-500 rpm.

7. The tear self-powered blood glucose monitoring contact lens according to claim 2, characterized in that: The total mixing time is 60 to 120 minutes.

8. The tear self-powered blood glucose monitoring contact lens according to claim 1, characterized in that: The substrate provides the optical function of the contact lens; The hydrovoltaic power generation devices can output a voltage large enough to supply the Bluetooth chip and the transimpedance amplifier circuit with work after being connected in series; The blood sugar detection module is composed of a three-electrode system, which converts the blood sugar concentration into a current signal, which is then converted into a voltage signal through a transimpedance amplifier circuit and output to the Bluetooth module; The energy management module is used to increase the current and assist in completing the information transmission; The hydrovoltaic power generation device is arranged at the bottom of the circuit.

9. The tear self-powered blood glucose monitoring contact lens according to claim 1, characterized in that: The circuit in the contact lens is arranged on the substrate in a fan-shaped shape, and the conical geometry of the contact lens is formed by merging the busbars at both ends of the fan-shaped. The curvature and taper of the contact lens are adjusted by changing the geometry of the adjustment sector and the position of the generatrix.

10. The tear self-powered blood glucose monitoring contact lens according to claim 1, characterized in that: The three-electrode system in the blood sugar detection module includes a working electrode, a reference electrode and a counter electrode; The working electrode and the counter electrode form a current loop, and the counter electrode plays a role in current conduction; The working electrode and the reference electrode form a voltage loop, the reference electrode serves as a reference for measuring or applying the potential of the working electrode, and the potential of the working electrode is the potential relative to the reference electrode; The surface of the working electrode is coated with glucose oxidase; Preferably, the material of the working electrode is platinum; The material of the reference electrode is silver; The material of the counter electrode is carbon.

Images