Multifunctional health monitoring contact lens and methods of making and detecting same
By integrating a Raman enhancement substrate, a three-electrode substrate, and a photonic crystal substrate into a contact lens, the problem of limited functionality in contact lenses is solved, enabling the integration of multiple detection methods and improving detection sensitivity and the functional versatility of contact lenses.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- WENZHOU MEDICAL UNIV
- Filing Date
- 2022-06-09
- Publication Date
- 2026-05-12
AI Technical Summary
Current contact lenses have limited functionality and cannot support multiple testing methods. Furthermore, existing testing methods suffer from problems such as being invasive, costly, inconvenient, or not providing real-time testing.
A Raman-enhanced substrate, a three-electrode substrate, and a photonic crystal substrate are integrated into a contact lens for quantitative detection of biomacromolecules, electrochemical detection of biomolecules, and visual detection of intraocular pressure, respectively. Multiple detection methods are achieved through changes in Raman scattering intensity, electrochemical methods, and spectral changes.
It enables label-free identification and quantitative detection of biomacromolecules, non-invasive real-time detection of small biomolecules, and visualized detection of intraocular pressure, improving detection sensitivity and the functional diversity and scalability of contact lenses.
Smart Images
Figure CN114878550B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of medical testing technology for contact lenses, and more particularly to a multifunctional health monitoring contact lens and its preparation and testing methods. Background Technology
[0002] Currently, an increasing number of people are choosing to wear contact lenses to correct their vision and improve their quality of life. Contact lenses, also known as corneal contact lenses, are lenses worn on the cornea of the eye to correct vision or protect the eyes. Compared to eyeglasses, contact lenses have higher optical transparency, and they also serve as an adjunct treatment, greatly improving the vision of patients with myopia, hyperopia, astigmatism, and other types of nearsightedness.
[0003] In existing technologies, contact lenses are limited to vision correction and have a single function. Conventional intraocular pressure (IOP) monitoring solutions include: commercial tonometers, invasive IOP sensors, and non-invasive IOP sensors. Among them, commercial tonometers mostly use point measurement, which are large, expensive, and lack portability, and cannot achieve 24-hour real-time dynamic IOP monitoring. Invasive IOP sensors can directly obtain IOP values, but the implantation process inevitably causes trauma to the patient. Non-invasive IOP sensors integrate the sensor with the contact lens or other devices. By attaching the sensor to the corneal surface, it monitors the deformation and tension of the cornea under changes in intraocular pressure to monitor IOP. However, the sensor is a complex electronic component integrated based on principles such as capacitance, inductance, and strain gauges, which may scratch the user's cornea during use.
[0004] Existing matrix metalloproteinase detection solutions include: ELISA kits and RPS InflammaDryDetector. Among them, ELISA kits are expensive and have complicated operation procedures; RPS InflammaDry Detector is a qualitative detection device for matrix metalloproteinase-9, but it cannot achieve quantitative detection of matrix metalloproteinase-9.
[0005] Existing blood glucose testing methods include: collecting peripheral venous blood by pricking a finger and monitoring blood glucose concentration through electrochemical detection; collecting venous blood and detecting blood glucose concentration through colorimetric reactions; and continuous glucose monitoring (CGM), a novel minimally invasive blood glucose monitoring method. Among these, all of the above blood glucose testing methods are invasive or minimally invasive, and the mainstream methods of collecting peripheral venous blood for electrochemical detection or directly collecting venous blood and detecting blood glucose concentration through colorimetric reactions cannot obtain real-time monitoring signals. Summary of the Invention
[0006] This invention provides a multifunctional health monitoring contact lens and its preparation and testing methods, which solves the shortcomings of the single function of contact lenses in the prior art. The multifunctional testing module integrates multiple testing methods to achieve qualitative and quantitative detection of relevant substances, improves the accuracy of testing, reduces the pain of users, and enhances the functional diversity and scalability of contact lenses.
[0007] This invention provides a multifunctional health monitoring contact lens, comprising a contact lens body, the contact lens body including a multifunctional detection module, the multifunctional detection module comprising:
[0008] A Raman-enhanced substrate is fixed on the iris region of the outer surface of the contact lens body. The Raman-enhanced substrate is modified with a specific polypeptide with a Raman tag to enhance the Raman scattering intensity change of the specific polypeptide, thereby realizing the quantitative detection of biomacromolecules in the solution to be detected.
[0009] A three-electrode substrate is fixedly disposed in the iris region at the outer edge of the contact lens body, and is used for quantitative detection of small biological molecules in the test solution based on an electrochemical method.
[0010] A photonic crystal substrate is fixedly disposed in the iris region of the contact lens body to achieve visual detection of intraocular pressure based on spectral changes of the photonic crystal substrate.
[0011] The multifunctional health monitoring contact lens provided by the present invention uses an opal-structured photonic crystal microsphere as a template to sputter a metal layer of a specific thickness, and then removes the template to obtain a metal nanostructure.
[0012] The multifunctional health monitoring contact lens provided by the present invention has a bowl-shaped metal nanostructure.
[0013] According to the multifunctional health monitoring contact lens provided by the present invention, the three-electrode substrate includes a working electrode, a counter electrode, and a reference electrode, wherein the working electrode is modified with an enzyme-containing PEDOT:PSS hydrogel, the counter electrode is modified with gold, and the reference electrode is modified with silver chloride.
[0014] The multifunctional health monitoring contact lens provided by the present invention includes a test solution comprising tears.
[0015] The multifunctional health monitoring contact lens provided by the present invention includes a photonic crystal substrate comprising an inverse opal structure photonic crystal hydrogel microsphere sensor.
[0016] The multifunctional health monitoring contact lens provided by the present invention uses an inverse opal structure photonic crystal hydrogel microsphere sensor, which is obtained by using opal structure photonic crystal microspheres as templates, polymerizing a hydrogel precursor solution containing monomers or functional groups in the gaps of the photonic crystal to form a hydrogel network, and then removing the template.
[0017] The multifunctional health monitoring contact lens provided by the present invention comprises one of the following: opal structure photonic crystal microspheres: silica nanoparticles, polymethyl methacrylate nanoparticles, and polystyrene nanoparticles.
[0018] This invention also provides a method for preparing a multifunctional health monitoring contact lens, comprising:
[0019] Preparation of Raman-enhanced substrate: A monolayer opal template is prepared at the air-water interface, and a metal layer of a specific thickness is deposited on the monolayer opal template to obtain an opal substrate with a metal layer covering. The opal substrate is flipped over and the monolayer opal template is removed to obtain a Raman-enhanced substrate, on which a specific polypeptide with a Raman tag is disposed.
[0020] Preparation of the three-electrode substrate: The contact lens body is attached with copper foil, and a copper substrate of the three-electrode system is prepared by etching. A layer of gold is electroplated on the counter electrode of the copper substrate of the three-electrode system, silver chloride paste is dropped onto the reference electrode, and enzyme-containing PEDOT:PSS hydrogel is modified on the working electrode to obtain the three-electrode substrate.
[0021] Preparation of photonic crystal substrate: An opal-structured photonic crystal template is added to a hydrogel precursor solution, an initiator is added, the hydrogel precursor solution is solidified, and the opal-structured photonic crystal template filled in the hydrogel precursor solution is removed. After washing with pure water, the photonic crystal substrate is prepared and embedded in the contact lens body. The hydrogel precursor solution is the material used to prepare the contact lens body.
[0022] The prepared Raman-enhanced substrate and three-electrode substrate are implanted into the iris region of the contact lens body.
[0023] This invention also provides a multifunctional health monitoring contact lens detection method, comprising:
[0024] Quantitative detection of biomacromolecules based on changes in Raman intensity: Under conditions of full contact between contact lenses and the solution to be tested, biomacromolecules in the solution to be tested are quantitatively detected based on the changes in Raman intensity of specific peptides before and after the reaction.
[0025] Quantitative detection of small biomolecules based on a three-electrode system: a first circuit is constructed by the working electrode and a reference electrode, and a second circuit is constructed by the working electrode and a counter electrode. The first and second circuits form a three-electrode substrate. The electrochemical detection of small biomolecules in the solution to be detected is achieved using the three-electrode substrate.
[0026] Intraocular pressure detection based on contact lens color: When contact lenses are in use, the reflectance spectrum of color changes in the contact lens image is acquired, and intraocular pressure is monitored based on the color changes of the contact lens.
[0027] This invention provides a multifunctional health monitoring contact lens and its preparation and detection methods. By detecting the change in Raman scattering intensity of specific peptides in a Raman-enhanced substrate before and after the contact lens reacts with the test solution, it achieves label-free identification and quantitative detection of biological macromolecules. This method is convenient, rapid, and exhibits high sensitivity for detecting substances present in extremely low concentrations in biological samples. Simultaneously, a microelectrode electrochemical method is used to detect small biological molecules in the test solution, enabling real-time, continuous, and non-invasive detection of human small biological molecules without side effects. The high sensitivity further enhances the detection sensitivity by enabling visual detection of intraocular pressure using a photonic crystal substrate, thus reducing costs. Furthermore, the multifunctional detection module within the contact lens integrates multiple detection methods and can be expanded to achieve qualitative and quantitative detection of relevant substances in tears, improving the functional diversity and scalability of the contact lens. Attached Figure Description
[0028] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.
[0029] Figure 1 This is one of the structural schematic diagrams of the multifunctional health monitoring contact lens provided by the present invention;
[0030] Figure 2 This is the second structural schematic diagram of the multifunctional health monitoring contact lens provided by the present invention;
[0031] Figure 3 This is a schematic diagram of matrix metalloproteinase-9 concentration detection provided by the present invention;
[0032] Figure 4 This is a schematic diagram of glucose concentration detection provided by the present invention;
[0033] Figure 5 This is a schematic diagram of intraocular pressure detection provided by the present invention. Detailed Implementation
[0034] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.
[0035] The following is combined Figure 1 This invention describes a multifunctional health monitoring contact lens.
[0036] This invention provides a multifunctional health monitoring contact lens. Figure 1 This is one of the structural schematic diagrams of the multifunctional health monitoring contact lens provided by the present invention, such as... Figure 1 As shown, the multifunctional health monitoring contact lens includes a contact lens body, and the contact lens body includes a multifunctional detection module 100. The multifunctional detection module 100 includes, but is not limited to:
[0037] Raman-enhancing substrate 101 is fixed on the iris region of the outer surface of the contact lens body. Raman-enhancing substrate 101 is modified with specific peptides with Raman tags to enhance the Raman scattering intensity change of the specific peptides and realize the quantitative detection of biomacromolecules in the solution to be detected.
[0038] The three-electrode substrate 102 is fixedly disposed in the iris region at the outer edge of the contact lens body and is used for quantitative detection of small biological molecules in the test solution based on an electrochemical method.
[0039] The photonic crystal substrate 103 is fixedly disposed in the iris area of the contact lens body and is used to realize the visual detection of intraocular pressure based on the spectral changes of the photonic crystal substrate.
[0040] Optionally, Figure 2 This is the second structural schematic diagram of the multifunctional health monitoring contact lens provided by the present invention, as shown below. Figure 2 As shown, the ring-shaped dashed area represents the iris region of the contact lens body. During the manufacturing process of the contact lens body, the photonic crystal substrate 103 is embedded in the iris region of the contact lens body. Even if the color of the photonic crystal substrate 103 changes due to changes in intraocular pressure, it will not affect the wearer's normal use, further improving the user experience. The Raman enhancement substrate 101 and the three-electrode substrate 102 are both embedded in the iris region of the contact lens body. After completely reacting with the tear fluid, they respectively realize the quantitative detection of biomacromolecules and biosmall molecules, making the detection convenient and greatly reducing the detection cost.
[0041] Optionally, the specific polypeptide has a specific sequence, which includes a pre-terminal segment, a middle segment, and a post-terminal segment. The pre-terminal segment is connected to the Raman-enhancing substrate, the middle segment can be recognized and cleaved by the corresponding biomolecule, and the post-terminal segment contains a Raman signal molecule. That is, the middle segment structure or length of the specific polypeptide differs for different biomolecules. After the Raman-enhancing substrate is in complete contact with the test solution, the biomolecules in the test solution recognize and cleave the middle segment of the specific polypeptide, causing the Raman signal molecule of the post-terminal segment to detach from the Raman-enhancing substrate. By judging the degree of weakening of the Raman signal molecule intensity, the number of cleaved specific polypeptides is determined, thereby realizing the quantitative detection of biomolecules. The middle segment structure of the specific polypeptide can be replaced according to the biomolecule to be detected. In addition, multiple specific polypeptides can be simultaneously connected to the Raman-enhancing substrate to realize the simultaneous detection of multiple biomolecules. Each specific polypeptide corresponds to one biomolecule, and the Raman signal molecules in the middle and post-terminal segments of each specific polypeptide are in one-to-one correspondence.
[0042] Furthermore, the aforementioned Raman signal molecules can be dye molecules, and the biomacromolecules can be various proteases, with the proteases having the function of recognizing and cleaving specific polypeptide intermediates.
[0043] Optionally, the solution to be tested includes tears for sufficient contact with the Raman-enhancing substrate 101.
[0044] Optionally, the Raman-enhanced substrate 101 is a metal nanostructure obtained by sputtering a metal layer of a specific thickness using opal-structured photonic crystal microspheres as a template and then removing the template. The metal nanostructure is bowl-shaped.
[0045] For example, the detection target can be modulated using a specific peptide. The detection target includes, but is not limited to, related proteases. Taking matrix metalloproteinase-9 (MMP-9) as an example, MMP-9 is a biomacromolecule, and its corresponding specific peptide sequence is: Tamra-Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-Cys. Here, Cys represents the front segment, used to connect to the Raman-enhancing substrate; Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg represents the middle segment; that is, MMP-9 recognizes and cleaves the middle segment Lys-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg; and Tamra represents the Raman signal molecule. The concentration information of MMP-9 is obtained by analyzing the heat dissipation spectrum using the Raman scattering effect enhanced by the specific peptide. The detection target can be designed based on actual needs and is not limited here.
[0046] In the above-mentioned specific polypeptide sequences, Cys represents cysteine, Tamra represents 5-carboxy-tetramethyl-rhodamine, Lys represents lysine, Pro represents proline, Leu represents leucine, Gly represents glycine, Dap (Dnp) represents 2,4-dinitrophenyl-L-2,3-diaminopropionic acid, Ala represents alanine, and Arg represents arginine.
[0047] Optionally, the three-electrode substrate 102 includes a working electrode, a counter electrode, and a reference electrode. The working electrode is modified with an enzyme-containing PEDOT:PSS hydrogel, which helps improve polymer chain extension to form a better conductive and nanoporous network. The counter electrode is modified with gold, and the reference electrode is modified with silver chloride. Here, PEDOT:PSS represents poly(3,4-ethylenedioxythiophene) / poly(styrenesulfonate) anion-doped poly(3,4-ethylenedioxythiophene).
[0048] For example, by using a three-electrode substrate to modify different types of enzymes, the detection target can be adjusted. The detection target includes, but is not limited to, glucose, and the blood glucose level can be quantitatively detected by detecting the glucose concentration.
[0049] Optionally, the photonic crystal substrate includes, but is not limited to, photonic crystal substrate 103.
[0050] Optionally, the photonic crystal substrate 103 is obtained by using opal-structured photonic crystal microspheres as templates, polymerizing a hydrogel precursor solution containing monomers or functional groups in the voids of the photonic crystal to form a hydrogel network, and then removing the template.
[0051] Optionally, the opal-structured photonic crystal microspheres include one of silica nanoparticles, polymethyl methacrylate nanoparticles, or polystyrene nanoparticles.
[0052] In addition, the multifunctional detection module 100 may also include a microprocessor chip and a wireless transmission module. The microprocessor chip can connect to the three-electrode substrate and the wireless transmission module, converting the electrochemical detection signal collected by the three-electrode substrate into an electrical signal, and then wirelessly transmitting it to a host computer for data analysis via the wireless transmission module. Figure 2As shown, the wireless transmission module may include wireless communication coils distributed in the iris area of the contact lens body, and may also include a wireless transmission microchip that can be embedded in the iris area of the contact lens body.
[0053] Furthermore, the multifunctional detection module 100 may also include a pH detection unit, further expanding the functionality of contact lenses and enabling multifunctional health monitoring of contact lenses.
[0054] The multifunctional health monitoring contact lens provided by this invention achieves label-free identification and quantitative detection of biological macromolecules by detecting changes in the Raman scattering intensity of specific peptides in a Raman-enhanced substrate before and after the contact lens reacts with a test solution. This is convenient, fast, and highly sensitive for detecting substances present in extremely low concentrations in biological samples. Simultaneously, a microelectrode electrochemical method is used to detect small biological molecules in the test solution, enabling real-time, continuous, and non-invasive detection of human small biological molecules without side effects. The high sensitivity further enhances the detection, and the photonic lens substrate allows for visualized intraocular pressure detection, improving sensitivity and reducing cost. Furthermore, the multifunctional detection module within the contact lens integrates multiple detection methods and can be expanded as needed to achieve qualitative and quantitative detection of related substances in tears, improving the functional diversity and scalability of the contact lens.
[0055] The following describes the preparation method of the multifunctional health monitoring contact lens provided by the present invention. The preparation method of the multifunctional health monitoring contact lens described below can be referred to in correspondence with the multifunctional health monitoring contact lens described above.
[0056] This invention also provides a method for preparing a multifunctional health monitoring contact lens, comprising:
[0057] Preparation of Raman-enhanced substrate 101: A monolayer opal template is prepared at the air-water interface, and a metal layer of a specific thickness is deposited on the monolayer opal template to obtain an opal substrate with a metal layer covering. The opal substrate is flipped over and the monolayer opal template is removed to obtain Raman-enhanced substrate 101, which has a specific polypeptide with a Raman tag.
[0058] Preparation of the three-electrode substrate 102: Copper foil is attached to the contact lens body, and a copper substrate of the three-electrode system is prepared by etching. A layer of gold is electroplated on the counter electrode of the copper substrate of the three-electrode system, silver chloride paste is dropped on the reference electrode, and enzyme-containing PEDOT:PSS hydrogel is modified on the working electrode to obtain the three-electrode substrate 102.
[0059] Preparation of photonic crystal substrate 103: An opal-structured photonic crystal template is added to a hydrogel precursor solution, an initiator is added, the hydrogel precursor solution is solidified, and the opal-structured photonic crystal template filled in the hydrogel precursor solution is removed. After washing with pure water, the photonic crystal substrate 103 is prepared and embedded in the contact lens body. The hydrogel precursor solution is the material used to prepare the contact lens body.
[0060] The prepared Raman-enhanced substrate 101 and three-electrode substrate 102 are implanted into the iris region of the contact lens body.
[0061] Optionally, the single-layer opal template is self-assembled and formed at the air-water interface, resulting in a Raman-enhanced substrate 101 with a nanobowl-shaped structure.
[0062] Optionally, the opal-structured photonic crystal template is assembled from monodisperse nanoparticles, and after the initiator is added, the curing method of the hydrogel precursor solution includes, but is not limited to, ultraviolet light irradiation or heating, and the photonic crystal substrate 103 is stored in pure water after preparation.
[0063] The multifunctional health monitoring contact lens preparation method provided by this invention achieves label-free identification and quantitative detection of biological macromolecules by detecting the change in Raman scattering intensity of specific peptides in a Raman-enhanced substrate before and after the contact lens reacts with the test solution. This method is convenient, fast, and highly sensitive for detecting substances with extremely low concentrations in biological samples. Simultaneously, a microelectrode electrochemical method is used to detect small biological molecules in the test solution, enabling real-time, continuous, and non-invasive detection of human small biological molecules without side effects. The high sensitivity further enhances the detection sensitivity by enabling visual detection of intraocular pressure using a photonic crystal substrate, thus reducing costs. Furthermore, the multifunctional detection module within the contact lens integrates multiple detection methods and can be expanded as needed to achieve qualitative and quantitative detection of relevant substances in tears, improving the functional diversity and scalability of the contact lens.
[0064] The following describes the detection method for the multifunctional health monitoring contact lens provided by the present invention. The preparation method of the multifunctional health monitoring contact lens described below can be referred to in correspondence with the multifunctional health monitoring contact lens and its preparation method described above.
[0065] This invention also provides a method for preparing a multifunctional health monitoring contact lens, comprising:
[0066] Quantitative detection of biomacromolecules based on changes in Raman intensity: Under conditions of full contact between contact lenses and the solution to be tested, biomacromolecules in the solution to be tested are quantitatively detected based on the changes in Raman intensity of specific peptides before and after the reaction.
[0067] Quantitative detection of small biomolecules based on a three-electrode system: The working electrode and the reference electrode form the first circuit, and the working electrode and the counter electrode form the second circuit. The first circuit and the second circuit form a three-electrode substrate 102. The three-electrode substrate 102 is used to perform electrochemical detection of small biomolecules in the solution to be detected, thereby achieving quantitative detection of small biomolecules.
[0068] Intraocular pressure detection based on contact lens color: When contact lenses are in use, the reflectance spectrum of color changes in the contact lens image is acquired, and intraocular pressure is monitored based on the color changes of the contact lens.
[0069] Optionally, a laser micro Raman spectroscopy or a portable Raman spectroscopy instrument can be used to detect the Raman intensity changes of the specific peptide before and after the reaction, and the concentration of matrix metalloproteinases can be quantified based on the changes in Raman intensity. Laser micro Raman spectroscopy or portable Raman spectroscopy is a rapid and sensitive spectroscopic analysis tool that can perform label-free identification and quantitative detection of different molecules. It offers high detection sensitivity and convenience, making it suitable for monitoring substances present in extremely low concentrations in biological samples, such as biomacromolecules like matrix metalloproteinases.
[0070] For example, Figure 3 This is a schematic diagram of matrix metalloproteinase-9 concentration detection provided by the present invention, as shown below. Figure 3 As shown, taking the detection of matrix metalloproteinase-9 concentration as an example, the normal concentration of matrix metalloproteinase-9 in tears is 3-40 ng / mL. The detection limit of the quantitative detection method for biological macromolecules based on the change of Raman intensity provided by this invention can reach 1.29 ng / mL, and the upper limit of linear detection can reach at least 1000 ng / mL.
[0071] Optionally, electrochemical methods include, but are not limited to, amperometric response, electrochemical impedance spectroscopy, and cyclic voltammetry. By comprehensively characterizing and analyzing the electrochemical properties of the prepared three-electrode substrate 102, the electrochemical detection effect of the three-electrode substrate 102 on glucose can be further obtained.
[0072] For example, Figure 4 This is a schematic diagram of glucose concentration detection provided by the present invention, as shown below. Figure 4 As shown, taking glucose concentration detection as an example, the normal blood glucose range in tears is 0.1-0.6 mM. The detection limit of the quantitative detection method for small biological molecules based on the three-electrode system provided by this invention can reach 0.01 mM, and the upper limit of linear detection can reach at least 10 mM.
[0073] Optionally, during the process of increased intraocular pressure after wearing contact lenses, the lattice spacing of the photonic crystal in the prepared inverse opal structure photonic crystal hydrogel changes, causing a color change. This provides a basis for visual detection, eliminating the need for labeling and achieving truly label-free detection. This greatly simplifies the detection tool, significantly reduces detection costs, and provides high detection sensitivity. Based on spectral colorimetry, by capturing images of the contact lenses, a reflectance spectrometer can be used to analyze the reflectance spectrum of the color changes in the contact lenses, allowing for real-time monitoring of intraocular pressure.
[0074] For example, Figure 5 This is a schematic diagram of intraocular pressure detection provided by the present invention, as shown below. Figure 5 As shown, the intraocular pressure range of normal glasses is 10-20 mmHg, while the intraocular pressure detection coverage range of the color-based contact lens detection method provided by this invention can reach 0-50 mmHg.
[0075] This invention provides a multifunctional health monitoring contact lens detection method that achieves label-free identification and quantitative detection of biological macromolecules by detecting changes in Raman scattering intensity of specific peptides in a Raman-enhanced substrate before and after the contact lens reacts with the test solution. This method is convenient, fast, and highly sensitive for detecting substances present in extremely low concentrations in biological samples. Simultaneously, a microelectrode electrochemical method is used to detect small biological molecules in the test solution, enabling real-time, continuous, and non-invasive detection of human small biological molecules without side effects. The high sensitivity further enhances the detection, and the photonic lens substrate allows for visualized intraocular pressure detection, improving sensitivity and reducing cost. Furthermore, the multifunctional detection module within the contact lens integrates multiple detection methods and can be expanded as needed to achieve qualitative and quantitative detection of related substances in tears, improving the functional diversity and scalability of the contact lens.
[0076] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims
1. A multifunctional health monitoring contact lens, comprising a contact lens body, characterized in that, The contact lens body includes a multi-functional detection module, which includes: A Raman-enhanced substrate is fixedly disposed in the central region of the iris area on the outer surface of the contact lens. The Raman-enhanced substrate is modified with a specific polypeptide bearing a Raman tag to enhance the Raman scattering intensity change of the specific polypeptide, enabling quantitative detection of biomolecules in the solution to be detected. Multiple specific polypeptides are simultaneously linked to the Raman-enhanced substrate, each specific polypeptide corresponding to a specific target biomolecule, and the intermediate recognition sequence of each specific polypeptide only specifically responds to the corresponding target biomolecule, enabling simultaneous detection of multiple biomolecules. A three-electrode substrate is fixed in the iris region of the annular area at the outer edge of the contact lens body for quantitative detection of small biological molecules in the test solution based on an electrochemical method. The three-electrode substrate includes a working electrode, a counter electrode, and a reference electrode. The working electrode is modified with an enzyme-containing PEDOT:PSS hydrogel optimized with a porous network, the counter electrode is modified with gold, and the reference electrode is modified with silver chloride. A photonic crystal substrate is fixedly disposed in the iris area of the inner side of the contact lens and embedded inside the lens, and is used to realize the visual detection of intraocular pressure based on the spectral changes of the photonic crystal substrate; The Raman-enhanced substrate is a bowl-shaped metal nanostructure obtained by sputtering a metal layer of a specific thickness onto an opal-structured photonic crystal microsphere as a template and then removing the template. The Raman-enhanced substrate has a detection limit of ≤1.29 ng / mL for biological macromolecules, the three-electrode substrate has a detection limit of ≤0.01 mM for biological small molecules, and the photonic crystal substrate has an intraocular pressure detection range of 0-50 mmHg.
2. The multifunctional health monitoring contact lens according to claim 1, characterized in that, The solution to be tested includes tears.
3. The multifunctional health monitoring contact lens according to claim 1, characterized in that, The photonic crystal substrate includes an inverse opal structure photonic crystal hydrogel microsphere sensor.
4. The multifunctional health monitoring contact lens according to claim 3, characterized in that, The inverse opal structure photonic crystal hydrogel microsphere sensor is obtained by using opal structure photonic crystal microspheres as templates, polymerizing a hydrogel precursor solution containing monomers or functional groups in the gaps of the photonic crystal to form a hydrogel network, and then removing the template.
5. The multifunctional health monitoring contact lens according to claim 4, characterized in that, The opal-structured photonic crystal microspheres include one of silica nanoparticles, polymethyl methacrylate nanoparticles, and polystyrene nanoparticles.
6. A method for preparing a multifunctional health monitoring contact lens, characterized in that, include: Preparation of Raman-enhanced substrate: A monolayer opal template is prepared at the air-water interface. Opal-structured photonic crystal microspheres are used as template supports, and a metal layer of a specific thickness is deposited on the monolayer opal template to obtain an opal substrate with a metal layer covering. The opal substrate is flipped over and the monolayer opal template is removed to obtain a bowl-shaped metal nanostructure Raman-enhanced substrate. The Raman-enhanced substrate is provided with specific peptides with Raman tags, and the preparation process of the Raman-enhanced substrate ensures that its detection limit for biomacromolecules is ≤1.29 ng / mL. Preparation of the three-electrode substrate: Copper foil is attached to the contact lens body, and a copper substrate of the three-electrode system is prepared by etching. A layer of gold is electroplated on the counter electrode of the copper substrate of the three-electrode system, and silver chloride paste is dropped onto the reference electrode. A porous network is constructed by controlling the degree of crosslinking of the hydrogel. The working electrode is modified with an enzyme-containing PEDOT:PSS hydrogel optimized by the porous network to obtain the three-electrode substrate. The preparation process of the three-electrode substrate ensures that its detection limit for small biological molecules is ≤0.01mM. Preparation of photonic crystal substrate: An opal-structured photonic crystal template is added to a hydrogel precursor solution, an initiator is added, the hydrogel precursor solution is solidified, and the opal-structured photonic crystal template filled in the hydrogel precursor solution is removed. After washing with pure water, the photonic crystal substrate is prepared. The photonic crystal substrate is embedded in the iris area of the inner side of the contact lens body. The hydrogel precursor solution is the material used to prepare the contact lens body. The preparation process of the photonic crystal substrate ensures that its intraocular pressure detection range is 0-50 mmHg. The prepared Raman-enhanced substrate is implanted into the central region of the iris area on the outer surface of the contact lens body, the three-electrode substrate is implanted into the annular region at the outer edge of the contact lens body, and the photonic crystal substrate is fixed to the iris area on the inner side of the contact lens body and kept embedded, thus completing the integration of the multifunctional detection module.
7. A multifunctional health monitoring contact lens detection method, characterized in that, include: Quantitative detection of biomacromolecules based on Raman intensity changes: With the contact lens in full contact with the test solution, biomacromolecules in the test solution are simultaneously and quantitatively detected based on the Raman intensity changes of multiple specific peptides before and after the reaction, ensuring that the detection limit for the biomacromolecules is ≤1.29 ng / mL; wherein, each of the multiple specific peptides corresponds to one target biomacromolecule, and the intermediate recognition sequence of each specific peptide only specifically responds to the corresponding target biomacromolecule; Quantitative detection of small biomolecules based on a three-electrode system: A first circuit is constructed using a working electrode and a reference electrode, and a second circuit is constructed using a working electrode and a counter electrode. The first and second circuits form a three-electrode substrate. The working electrode is modified with an enzyme-containing PEDOT:PSS hydrogel optimized with a porous network. Electrochemical detection of small biomolecules in the solution to be detected is achieved using the three-electrode substrate. The quantitative detection of small biomolecules is realized through the synergistic effect of potential calibration in the first circuit and current acquisition in the second circuit. This detection method ensures that the detection limit for small biomolecules is ≤0.01mM. Intraocular pressure detection based on contact lens color: When the contact lens is in use, the reflectance spectrum corresponding to the color change of the photonic crystal substrate embedded inside the lens and located in the inner iris region of the contact lens is acquired. The change in reflectance spectrum is linearly related to the change in intraocular pressure, and the visual monitoring of intraocular pressure in the range of 0-50 mmHg is achieved based on the reflectance spectrum corresponding to the color change of the contact lens.