CN-114878550-B - Multifunctional health monitoring contact lens and preparation and detection methods thereof

CN114878550BCN 114878550 BCN114878550 BCN 114878550BCN-114878550-B

Abstract

The invention provides a multifunctional health monitoring contact lens and a preparation and detection method thereof, wherein the contact lens comprises a contact lens body, the contact lens body comprises a multifunctional detection module, the multifunctional detection module comprises a Raman enhancement substrate, a three-electrode substrate, a photonic crystal substrate and a photonic crystal substrate, wherein the Raman enhancement substrate is fixedly arranged in an iris area of the outer surface of the contact lens body, the Raman enhancement substrate is modified with specific polypeptide with a Raman tag and used for realizing quantitative detection of biological macromolecules in a solution to be detected based on Raman scattering intensity change of the surface enhancement specific polypeptide, the three-electrode substrate is fixedly arranged in the iris area at the outer edge of the contact lens body and used for quantitatively detecting biological micromolecules in the solution to be detected based on an electrochemical method, and the photonic crystal substrate is fixedly arranged in the iris area of the contact lens body and used for realizing visual detection of intraocular pressure based on spectral change of the photonic crystal substrate. The invention can realize qualitative and quantitative detection of related substances, is convenient and accurate, and improves the functional diversity and expandability of the contact lens.

Inventors

WANG YI
LIU XIAOHU
ZHANG QINGWEN
YE YING
XU CHANGSHUN

Assignees

温州医科大学

Dates

Publication Date: 20260512
Application Date: 20220609

Claims (7)

1. The utility model provides a multi-functional health monitoring contact lens, includes the contact lens body, its characterized in that, the contact lens body includes multi-functional detection module, multi-functional detection module includes: The Raman enhancement substrate is fixedly arranged in the middle area of the iris area on the outer surface of the contact lens body, and the Raman enhancement substrate is modified with specific polypeptide with a Raman label and is used for surface enhancing the Raman scattering intensity change of the specific polypeptide so as to realize quantitative detection of biological macromolecules in the solution to be detected; the Raman enhanced substrate is simultaneously connected with a plurality of specific polypeptides, each specific polypeptide corresponds to a target biological macromolecule, and the middle section recognition sequence of each specific polypeptide only specifically responds to the corresponding target biological macromolecule, so that the simultaneous detection of a plurality of biological macromolecules is realized; The three-electrode substrate is fixedly arranged in an iris area of an annular area at the outer edge of the contact lens body and is used for quantitatively detecting biological micromolecules in a solution to be detected based on an electrochemical method, and comprises a working electrode, a counter electrode and a reference electrode, wherein the working electrode is modified by enzyme-containing PEDOT (polyether-ether-ketone) PSS hydrogel optimized through a porous network, the counter electrode is modified by gold, and the reference electrode is modified by silver chloride; The photonic crystal substrate is fixedly arranged in the iris region of the inner side region of the contact lens body and embedded into the lens, and is used for realizing visual detection of intraocular pressure based on spectral change of the photonic crystal substrate; The Raman enhanced substrate is a bowl-shaped metal nano structure obtained by taking a photonic crystal microsphere with an opal structure as a template, sputtering a metal layer with a specific thickness and removing the template; The detection limit of the Raman enhanced substrate on biological macromolecules is less than or equal to 1.29ng/mL, the detection limit of the three-electrode substrate on biological small molecules is less than or equal to 0.01mM, and the intraocular pressure detection range of the photonic crystal substrate is 0-50mmHg.
2. The multi-purpose health monitoring contact lens of claim 1, wherein the solution to be tested comprises tears.
3. The multi-functional health monitoring contact lens of claim 1, wherein the photonic crystal substrate comprises an inverse opal structured photonic crystal hydrogel microsphere sensor.
4. The multifunctional health monitoring contact lens according to claim 3, wherein the inverse opal structured photonic crystal hydrogel microsphere sensor is obtained by taking opal structured photonic crystal microspheres as templates, polymerizing hydrogel precursor solutions containing monomers or functional groups in the gaps of the photonic crystals to form a hydrogel network, and then removing the templates.
5. The multi-functional health monitoring contact lens of claim 4, wherein the opal structured photonic crystal microsphere comprises one of silica nanoparticles, polymethyl methacrylate nanoparticles, polystyrene nanoparticles.
6. A method for preparing a multifunctional health monitoring contact lens, comprising the steps of: Preparing a single-layer opal template on an air-water interface, taking a opal structure photon crystal microsphere as a template support, depositing a metal layer with a specific thickness on the single-layer opal template to obtain a opal substrate covered by the metal layer, turning over the opal substrate and removing the single-layer opal template to obtain a bowl-shaped metal nano-structure Raman enhancement substrate, wherein the Raman enhancement substrate is provided with specific polypeptides with Raman labels, and the preparation process of the Raman enhancement substrate ensures that the detection limit of the Raman enhancement substrate on biological macromolecules is less than or equal to 1.29ng/mL; Preparing a three-electrode substrate, namely attaching copper foil to a contact lens body, preparing a copper substrate of a three-electrode system by adopting an etching method, electroplating a layer of gold on a counter electrode of the copper substrate of the three-electrode system, dripping silver chloride paste on a reference electrode, constructing a porous network by regulating and controlling the crosslinking degree of hydrogel, modifying enzyme-containing PEDOT (polyether-ether-ketone) PSS hydrogel optimized by the porous network on a working electrode, obtaining the three-electrode substrate, and ensuring that the detection limit of the three-electrode substrate on biological small molecules is less than or equal to 0.01mM by adopting the preparation process of the three-electrode substrate; Adding an opal structure photonic crystal template into a hydrogel prepolymer solution, adding an initiator, solidifying the hydrogel prepolymer solution, removing the opal structure photonic crystal template filled in the hydrogel prepolymer solution, washing with pure water, and finishing the preparation of the photonic crystal substrate, wherein the photonic crystal substrate is embedded into an iris region of an inner side region of a contact lens body, the hydrogel prepolymer solution is a preparation material of the contact lens body, and the preparation process of the photonic crystal substrate ensures that the intraocular pressure detection range of the photonic crystal substrate is 0-50mmHg; And implanting the prepared Raman enhanced substrate into the middle area of the iris area on the outer surface of the contact lens body, implanting the three-electrode substrate into the annular area at the outer edge of the contact lens body, and fixing the photonic crystal substrate in the iris area on the inner side area of the contact lens body and keeping an embedded state to complete the integration of the multifunctional detection module.
7. A method for detecting a multifunctional health monitoring contact lens, comprising: Quantitatively detecting biological macromolecules based on the change of Raman intensity, namely synchronously and quantitatively detecting the biological macromolecules in the solution to be detected based on the Raman intensity change data of various specific polypeptides before and after the reaction under the condition that the contact lens is fully contacted with the solution to be detected, wherein the detection limit of the biological macromolecules is less than or equal to 1.29ng/mL, each specific polypeptide in the various specific polypeptides corresponds to one target biological macromolecule, and the middle section recognition sequence of each specific polypeptide only responds to the corresponding target biological macromolecule specifically; The method comprises the steps of quantitatively detecting biological small molecules based on a three-electrode system, wherein a first loop is constructed by a working electrode and a reference electrode, a second loop is constructed by a working electrode and a counter electrode, a three-electrode substrate is formed by the first loop and the second loop, the working electrode is modified by enzyme-containing PEDOT (polyether-ketone) PSS hydrogel optimized through a porous network, electrochemical detection of the biological small molecules in a solution to be detected is realized by utilizing the three-electrode substrate, and quantitative detection of the biological small molecules is realized by the cooperation of potential calibration of the first loop and current acquisition of the second loop, and the detection limit of the biological small molecules is ensured to be less than or equal to 0.01mM; The method comprises the steps of detecting intraocular pressure based on the color of the contact lens, acquiring a reflection spectrum corresponding to the color change of an image of a photonic crystal substrate embedded into the lens and located in an iris region of an inner side region on a contact lens body when the contact lens is in a wearing state, wherein the reflection spectrum change and the intraocular pressure change are in a linear corresponding relation, and realizing visual monitoring of the intraocular pressure within a range of 0-50mmHg based on the reflection spectrum corresponding to the color change of the contact lens.

Description

Multifunctional health monitoring contact lens and preparation and detection methods thereof Technical Field The invention relates to the technical field of medical detection of contact lenses, in particular to a multifunctional health monitoring contact lens and a preparation and detection method thereof. Background Currently, more and more people choose to add to a line of contact lenses for correcting vision and improving quality of daily life. Contact lenses, also known as corneal contact lenses, are lenses worn on the cornea of an eyeball to correct vision or protect the eye. Compared with the frame glasses, the contact lens has higher optical transparency, and is also used as an auxiliary treatment means, thereby bringing great improvement to myopic patients with myopia, hyperopia, astigmatism and the like. In the prior art, the contact lens is limited to correcting vision, the function is single, the conventional intraocular pressure monitoring scheme comprises a commercial intraocular pressure meter, an invasive intraocular pressure sensor and a non-invasive intraocular pressure sensor, wherein most of the commercial intraocular pressure meter adopts point measurement, the commercial intraocular pressure meter is large in size, high in cost and lack of portability, real-time dynamic intraocular pressure monitoring cannot be realized for 24 hours, the invasive intraocular pressure sensor can directly obtain an intraocular pressure value, but the invasive intraocular pressure sensor inevitably causes wounds to a patient in the implantation process, the non-invasive intraocular pressure sensor is integrated with the contact lens or other devices, the intraocular pressure sensor is attached to the surface of a cornea, deformation and tension of the cornea under the condition of monitoring intraocular pressure change are monitored, and the sensor is a complex electronic component integrated based on the principles of capacitance, inductance, strain gauge and the like, so that the cornea of a user can be scratched in the use process. The existing matrix metalloproteinase detection scheme comprises an ELISA detection kit and a RPS INFLAMMADRY Detector, wherein the ELISA detection kit is high in price and complex in operation steps, and the RPS INFLAMMADRY Detector is a qualitative detection device of matrix metalloproteinase-9, so that quantitative detection of the matrix metalloproteinase-9 cannot be realized. The existing blood glucose detection scheme comprises a novel minimally invasive blood glucose monitoring mode of collecting peripheral venous blood by a finger and detecting blood glucose level through an electrochemical detection mode, detecting blood glucose concentration by collecting venous blood through a chromogenic reaction and dynamic blood glucose monitoring (CGM), wherein the various blood glucose detection methods are invasive or minimally invasive, and real-time monitoring signals cannot be obtained in the mainstream mode of detecting blood glucose through collecting peripheral venous blood electrochemically or directly collecting venous blood through a chromogenic reaction. Disclosure of Invention The invention provides a multifunctional health monitoring contact lens and a preparation and detection method thereof, which are used for solving the defect of single function of the contact lens in the prior art, and integrating a plurality of detection methods in a multifunctional detection module to realize qualitative and quantitative detection of related substances, improve detection accuracy, alleviate pain of a user and improve functional diversity and expandability of the contact lens. The invention provides a multifunctional health monitoring contact lens, which comprises a contact lens body, wherein the contact lens body comprises a multifunctional detection module, and the multifunctional detection module comprises: The Raman enhancement substrate is fixedly arranged in an iris region on the outer surface of the contact lens body, and the Raman enhancement substrate is modified with specific polypeptide with a Raman label and is used for surface enhancing the Raman scattering intensity change of the specific polypeptide so as to realize quantitative detection of biological macromolecules in a solution to be detected; The three-electrode substrate is fixedly arranged in an iris area at the outer edge of the contact lens body and is used for quantitatively detecting biological small molecules in the solution to be detected based on an electrochemical method; and the photonic crystal substrate is fixedly arranged in the iris region of the contact lens body and is used for realizing visual detection of intraocular pressure based on spectral change of the photonic crystal substrate. According to the multifunctional health monitoring contact lens provided by the invention, the Raman enhanced substrate is a metal nano structure obtained by taking the opal structure photon crystal microsp