Soft corneal contact lens and application thereof in infrared vision imaging detection

Abstract

The invention provides a soft corneal contact lens and application thereof in infrared vision imaging detection.The soft corneal contact lens comprises up-conversion gold nanoparticles Au / NaGdF4: Yb < 3 + >, Er < 3 + > and poly (2-hydroxyethyl methacrylate), and the soft corneal contact lens is used for converting near-infrared light with the wavelength ranging from 780 nm to 1100 nm into light visible to an object to be detected; the infrared vision imaging detection method comprises the following steps: determining a sensing threshold value of a to-be-detected object to near-infrared light intensity by detecting a recognition reaction result of the to-be-detected object wearing a soft corneal contact lens to near-infrared light; performing a near-infrared light time resolution test on the to-be-tested object, and determining time resolution identification information of the to-be-tested object on near-infrared light; and obtaining a detection result in infrared vision imaging based on the soft corneal contact lens according to the near-infrared light intensity sensing threshold and the time resolution identification information.

Description

Technical Field

[0001] The invention relates to the field of infrared imaging and visual science detection, and in particular to a soft corneal contact lens and application thereof in infrared visual imaging detection. Background Art

[0002] Imaging vision is one of the most important ways for organisms, including humans, to obtain information from the outside world. It plays an important role in their life activities, such as obtaining food, mating, distinguishing directions, and avoiding natural enemies. Mammals cannot see infrared light, which is determined by the inherent physical and chemical properties of photosensitive proteins in photoreceptor cells. For infrared light > 700 nm, due to its low photon energy, if the light in this band is to be perceived, the photosensitive protein must lower the energy threshold, resulting in a lot of thermodynamic noise. Therefore, this limitation means that mammals in nature do not have the ability of near-infrared light image vision.

[0003] Therefore, there is a need for a method to achieve infrared visual imaging through auxiliary means and to detect the effectiveness and reliability of infrared visual imaging. Summary of the invention

[0004] In view of this, in order to at least partially solve at least one of the above-mentioned technical problems, the present invention provides a soft corneal contact lens and its application in infrared visual imaging detection.

[0005] According to an embodiment of one aspect of the present invention, there is provided an application of a soft corneal contact lens in infrared visual imaging detection, wherein the soft corneal contact lens comprises upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ and poly(2-hydroxyethyl methacrylate), the soft contact lens is used to convert near-infrared light with a wavelength of 780 nm to 1100 nm into light visible to the subject to be tested;

[0006] Infrared visual imaging detection methods include:

[0007] By detecting the recognition reaction result of the test object wearing the soft corneal contact lens to the near-infrared light, the perception threshold of the test object to the near-infrared light intensity is determined;

[0008] When it is determined that the object to be tested responds to the near-infrared light according to the perception threshold of the object to be tested for the near-infrared light intensity, a near-infrared light time resolution test is performed on the object to be tested to determine the time resolution identification information of the object to be tested for the near-infrared light;

[0009] The detection results of soft corneal contact lenses in infrared visual imaging are obtained according to the near-infrared light intensity perception threshold and time resolution recognition information.

[0010] According to another embodiment of the present invention, there is provided a soft corneal contact lens, comprising:

[0011] Soft contact lenses including upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ and poly(2-hydroxyethyl methacrylate); wherein the upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ The mass concentration is 0.1%~10%.

[0012] According to an embodiment of the present invention, by including up-conversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ The soft corneal contact lens made of poly(2-hydroxyethyl methacrylate) can enable mammals to obtain near-infrared vision function simply, conveniently and without damage. At the same time, it has good biocompatibility and is compatible with upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ Poly(2-hydroxyethyl methacrylate), a polymer material with a refractive index close to that of conventional contact lenses, can increase the transmittance of soft contact lenses without affecting the normal transmittance of visible light imaging. By subjecting the subjects wearing soft contact lenses to different near-infrared light stimulations, the near-infrared visual ability of the subjects can be tested, and the response speed and dynamic visual ability of the individual to changes in infrared light are evaluated based on the measured perception threshold. The response speed and dynamic visual ability of the individual to changes in infrared light are evaluated based on the time resolution information, thereby evaluating the infrared visual ability. In this way, the infrared visual ability of the subjects can be comprehensively and objectively evaluated, and infrared imaging can be further applied to the fields of medicine and military, which is helpful to improve the infrared information recognition ability of mammals in natural environments and other infrared information environments. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The above and other objects, features and advantages of the present invention will become more apparent through the following description of the embodiments of the present invention with reference to the accompanying drawings, in which:

[0014] Figure 1 This is a schematic diagram of the method flow of infrared visual imaging detection according to an embodiment of the present invention;

[0015] Figure 2 This is a scanning electron microscope image of upconversion nano-gold particles according to an embodiment of the present invention;

[0016] Figure 3 This is the Fourier transform infrared spectrum of the up-conversion nano-gold particles in the embodiment of the present invention;

[0017] Figure 4This is a graph showing the refractive index test results of upconversion nanoparticles at different mass concentrations according to an embodiment of the present invention;

[0018] Figure 5 This is a result diagram of solvent screening by refractive index matching in an embodiment of the present invention;

[0019] Figure 6 This is a comparison chart of the transparency of different solvents in the embodiments of the present invention;

[0020] Figure 7 The present invention is a flow chart of the preparation of a soft corneal contact lens according to an embodiment of the present invention;

[0021] Figure 8 A diagram of a soft corneal contact lens prepared according to an embodiment of the present invention;

[0022] Fig. 9 This is a comparison diagram of the full electroretinogram response of mice in the embodiment of the present invention to near-infrared light;

[0023] Fig.10 This is a graph showing the pupil light reflex ability test results of mice wearing soft corneal contact lenses according to an embodiment of the present invention;

[0024] Fig.11 This is a diagram showing the results of the image visual pathway detection of near-infrared light by mice wearing soft corneal contact lenses according to an embodiment of the present invention;

[0025] Fig.12 This is a diagram showing the results of the image visual pathway detection of near-infrared light by mice wearing soft corneal contact lenses according to an embodiment of the present invention;

[0026] Fig.13 This is a schematic diagram of a test of a near-infrared light intensity perception threshold of a person to be tested according to an embodiment of the present invention;

[0027] Fig.14 This is a graph showing the test result of the perception threshold of near-infrared light intensity of a person to be tested according to an embodiment of the present invention;

[0028] Fig.15 This is a graph showing the time resolution test result of near-infrared light for a person under test according to an embodiment of the present invention;

[0029] Fig.16 This is a graph showing the spatial resolution test results of near-infrared light for a person under test in an embodiment of the present invention. DETAILED DESCRIPTION

[0030] Below, embodiments of the present invention will be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the present invention. In the following detailed description, for ease of explanation, many specific details are set forth to provide a comprehensive understanding of embodiments of the present invention. However, it is apparent that one or more embodiments may also be implemented without these specific details. In addition, in the following description, descriptions of known structures and technologies are omitted to avoid unnecessary confusion of concepts of the present invention.

[0031] The terms used herein are only for describing specific embodiments and are not intended to limit the present invention. The term "comprising" used herein indicates the existence of features, steps, operations, but does not exclude the existence or addition of one or more other features.

[0032] In the case of using expressions such as "at least one of A, B, and C, etc.", it should generally be interpreted in accordance with the meaning of the expression generally understood by those skilled in the art (for example, "a system having at least one of A, B, and C" should include but is not limited to a system having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, C, etc.). In the case of using expressions such as "at least one of A, B, or C, etc.", it should generally be interpreted in accordance with the meaning of the expression generally understood by those skilled in the art (for example, "a system having at least one of A, B, or C" should include but is not limited to a system having A alone, B alone, C alone, A and B, A and C, B and C, and / or A, B, C, etc.).

[0033] In the process of realizing the concept of the present invention, it was found that in order to expand the imaging visual spectrum range of mammals, upconversion nanoparticles specifically bound to photoreceptor cells were used in related technologies to achieve mammalian near-infrared light image vision, which opened up research on unconventional vision of animals. However, such upconversion nanoparticles need to be injected into the retinal photoreceptor layer to achieve the conversion of near-infrared light in the photoreceptor layer to visible light, so that mice can obtain near-infrared vision. However, this invasive injection method makes it difficult for the realization of near-infrared vision to be widely used.

[0034] Commonly used methods to enhance visual function mainly include contact lenses and frame glasses. Contact lenses refer to contact lenses, including hard contact lenses and invisible contact lenses. Hard contact lenses are usually made of materials containing fluorine and silicone polymers. The material is relatively hard. When worn on the cornea, it is not easy to change with the shape of the cornea, and it takes about 1 to 2 weeks to adapt to wearing. Soft contact lenses are usually made of hydrogel and silicone hydrogel. The water content of most lenses is above 30%. The lenses are soft and elastic, and are more comfortable to wear. Therefore, in daily life, the use of soft lenses is more common.

[0035] Taking into account the characteristics of soft corneal contact lenses that are widely used and non-invasive in life, the present invention integrates upconversion nanoparticles into the preparation materials of soft corneal contact lenses, and provides a soft corneal contact lens that can realize near-infrared vision in mice and humans. It has high biocompatibility and can realize near-infrared vision in humans conveniently and safely.

[0036] Specifically, according to an embodiment of one aspect of the present invention, there is provided an application of a soft corneal contact lens in infrared visual imaging detection, wherein the soft corneal contact lens comprises upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ and poly(2-hydroxyethyl methacrylate), the soft contact lens is used to convert near-infrared light with a wavelength of 780 nm to 1100 nm into light visible to the subject to be tested;

[0037] Infrared visual imaging detection methods, such as Figure 1 As shown, it includes steps S1 to S3:

[0038] Step S1: determining the perception threshold of the near-infrared light intensity of the test subject by detecting the recognition reaction result of the test subject wearing the soft corneal contact lens to the near-infrared light;

[0039] Step S2: when it is determined that the object to be tested responds to the near-infrared light according to the perception threshold of the object to be tested to the near-infrared light intensity, a near-infrared light time resolution test is performed on the object to be tested to determine the time resolution identification information of the object to be tested to the near-infrared light;

[0040] Step S3: obtaining a detection result based on the soft corneal contact lens in infrared visual imaging according to the near-infrared light intensity perception threshold and time resolution identification information.

[0041] According to an embodiment of the present invention, upconversion nanoparticles (UCNPs) are a special type of nanomaterials that have unique optical properties, namely, they can convert low-energy light such as near-infrared light into high-energy light such as visible light or ultraviolet light.

[0042] According to an embodiment of the present invention, the perception threshold of near-infrared light intensity refers to the minimum intensity of near-infrared light that can be perceived by the object to be tested. The perception threshold is an indicator of visual sensitivity, that is, how much light intensity must be reached in order to be perceived by the object to be tested; it refers to the shortest time interval between two consecutive stimuli that the object to be tested can distinguish. In the field of vision, temporal resolution refers to the minimum time interval that can identify rapidly changing or flickering light, such as flashing once every 5 seconds or 10 seconds, to determine whether the object to be tested can be identified.

[0043] According to an embodiment of the present invention, by including up-conversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ The soft corneal contact lens made of poly(2-hydroxyethyl methacrylate) can enable mammals to obtain near-infrared vision function simply, conveniently and without damage. At the same time, it has good biocompatibility and is compatible with upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ Poly(2-hydroxyethyl methacrylate), a polymer material with a refractive index close to that of conventional contact lenses, can increase the transmittance of soft contact lenses without affecting the normal transmittance of visible light imaging. By subjecting the subjects wearing soft contact lenses to different near-infrared light stimulations, the near-infrared visual ability of the subjects can be tested, and the response speed and dynamic visual ability of the individual to changes in infrared light are evaluated based on the measured perception threshold. The response speed and dynamic visual ability of the individual to changes in infrared light are evaluated based on the time resolution information, thereby evaluating the infrared visual ability. In this way, the infrared visual ability of the subjects can be comprehensively and objectively evaluated, and infrared imaging can be further applied to the fields of medicine and military, which is helpful to improve the infrared information recognition ability of mammals in natural environments and other infrared information environments.

[0044] According to an embodiment of the present invention, in step S1, by detecting the recognition reaction result of the object to be tested wearing a soft corneal contact lens to near-infrared light, determining the perception threshold of the object to be tested to the near-infrared light intensity includes steps S11 to S14:

[0045] Step S11: applying first near-infrared light stimulation of multiple light intensities to the object to be measured, wherein the first near-infrared light stimulation is applied in a preset mode;

[0046] Step S12: detecting the response behavior of the object to be tested to the first near-infrared light stimulus to obtain a first response result;

[0047] Step S13: matching the first response result with a preset pattern to determine a first matching result;

[0048] Step S14: determining the perception threshold of the object to be tested for the near-infrared light intensity according to a plurality of first matching results corresponding to the first near-infrared light stimuli of a plurality of light intensities.

[0049] According to an embodiment of the present invention, the preset mode refers to the mode of applying infrared light, such as applying it once every 5 seconds to a mouse, or once every 3 seconds to a person to be tested. The first matching result includes a match and a mismatch. If the preset mode and the response of the person to be tested are consistent, for example, the stimulation mode orally stated by the person to be tested is the same as the preset mode, then it is considered a match, otherwise it is a mismatch; or when the object to be tested is a mouse, in the presence or absence of near-infrared light stimulation, it is determined whether the visual perception of the mouse has a response, such as a full electroretinogram, or a pupil light reflex ability, or an image visual pathway. The perception threshold for near-infrared light intensity can be a specific light intensity value. For example, the light intensity can be 0, that is, there is no near-infrared light stimulation, or it can be a light intensity photon number / square micron of 1.5×10 6 wait.

[0050] According to an embodiment of the present invention, by applying a first near-infrared light stimulus of multiple light intensities and detecting the response behavior of the object to be tested, an accurate near-infrared light intensity perception threshold can be obtained, and customized light intensity perception data can be provided for the object to be tested, which is helpful for evaluating and improving visual function; by matching the first response result with a preset pattern, the response behavior of the object to be tested can be quantitatively analyzed, which is helpful for more accurately understanding the individual's reaction to near-infrared light. Determining the perception threshold of the object to be tested for near-infrared light intensity through multiple first matching results can improve the accuracy of infrared visual imaging detection and provide a more accurate near-infrared light perception ability assessment for the object to be tested.

[0051] According to an embodiment of the present invention, in step S2, performing a near-infrared light time resolution test on the object to be tested, and determining the time resolution identification information of the object to be tested for the near-infrared light includes steps S21 to S24:

[0052] Step S21: applying a second near-infrared light stimulus of multiple frequency modes to the object to be measured, wherein the frequency mode is a stroboscopic mode of a combination of continuous light and flashing light, or a stroboscopic mode of continuous light alone;

[0053] Step S22: detecting the response behavior of the object to be tested to the second near-infrared light stimulus to obtain a second response result;

[0054] Step S23: matching the second response result with the frequency pattern to determine a second matching result;

[0055] Step S24: determining the time resolution identification information of the object to be tested for the near-infrared light according to a plurality of second matching results corresponding to the second near-infrared light stimulation of a plurality of frequency modes.

[0056] According to an embodiment of the present invention, the frequency mode refers to infrared light emission modes of different frequencies, such as applying infrared light to mice once every 5 seconds, or once every 10 seconds; and for example, applying infrared light stimulation of two seconds and different combinations of flashing light to the person being tested.

[0057] According to an embodiment of the present invention, by applying a second near-infrared light stimulus of a different frequency mode and detecting the response behavior of the object to be measured, the temporal resolution of the object to be measured to near-infrared light can be accurately evaluated and the sensitivity and accuracy of the response characteristics of the object to be measured can be improved, and a comprehensive analysis can be performed to fully detect and understand the response characteristics of the object to be measured to near-infrared light stimulation.

[0058] According to an embodiment of the present invention, when the object to be detected is a person to be detected, the infrared visual imaging detection method further includes step S4.

[0059] Step S4: performing a near-infrared light spatial resolution test on the person to be tested to determine the spatial resolution identification information of the person to be tested for near-infrared light.

[0060] According to an embodiment of the present invention, through the near-infrared light spatial resolution test, the spatial resolution recognition information of the person to be tested for near-infrared light can be determined more accurately. The spatial resolution test helps to optimize the performance of the infrared visual imaging system. By improving the imaging quality, the visual response of the person to be tested can be captured more clearly, thereby improving the reliability and practicality of the detection scheme.

[0061] In some specific embodiments of the present invention, in step S4, the near-infrared light spatial resolution test of the person to be tested is performed to determine the spatial resolution identification information of the person to be tested for the near-infrared light, including steps S41 to S44:

[0062] Step S41: applying a third near-infrared light stimulus having a plurality of preset patterns to the persons to be tested;

[0063] Step S42: detecting the response behavior of the person to be tested to the third near-infrared light stimulation, and obtaining a third response result;

[0064] Step S43: matching the third response result with the preset pattern to determine a third matching result;

[0065] Step S44: determining the spatial resolution identification information of the person to be tested for near-infrared light according to a plurality of third matching results corresponding to the third near-infrared light stimulation of a plurality of preset patterns.

[0066] According to an embodiment of the present invention, near-infrared light spatial resolution refers to the ability of the person to be tested to distinguish different spatial positions or details in near-infrared light, as an indicator of the ability of the visual system to recognize image details. Preset graphics refer to known patterns or shapes used in the test, which are used to stimulate the visual system of the person to be tested to evaluate its spatial resolution, such as using different English letters or different shapes as preset graphics. Response behavior refers to the reaction of the person to be tested to the applied near-infrared light stimulation, such as pointing out the graphics seen, selecting the correct pattern, or describing the observed details. Matching refers to the process of comparing the response result of the person to be tested with the preset graphics to determine whether the response is correct or whether specific spatial details can be recognized; the third matching result refers to the result after the response result is matched with the preset graphics, indicating whether the response of the person to be tested is consistent with the expected graphics, which may specifically include matching or mismatching. Spatial resolution identification information refers to data or information about the ability of the person to be tested to the near-infrared light spatial resolution obtained based on the matching results of the person to be tested.

[0067] According to an embodiment of the present invention, by applying near-infrared light stimulation having multiple preset patterns and detecting the response behavior of the object to be tested, its spatial resolution recognition capability for near-infrared light can be evaluated, and the matching process can effectively associate the response result with the preset pattern, thereby determining a third matching result, thereby improving the efficiency of identifying the reaction of the person to be tested to different near-infrared light stimulations, and by integrating multiple matching results corresponding to the third near-infrared light stimulation of multiple preset patterns, the spatial resolution recognition information of the person to be tested to near-infrared light can be determined, and this comprehensive analysis capability is helpful to comprehensively detect the response characteristics of the person to be tested to near-infrared light stimulation.

[0068] In some specific embodiments of the present invention, in step S2, when the object to be tested is a mouse, a near-infrared light time resolution test is performed on the object to be tested, and determining the time resolution identification information of the object to be tested for the near-infrared light includes:

[0069] placing a behavior-trained mouse wearing a soft corneal contact lens in a box having a first area and a second area, wherein a passage is provided between the first area and the second area for the mouse to move; and the behavior-trained mouse has the behavior ability to avoid visible light;

[0070] Applying near-infrared light stimulation of multiple frequency modes to the first area or the second area;

[0071] Obtain behavioral data of behaviorally trained mice wearing soft contact lenses to distinguish near-infrared light of multiple light intensities;

[0072] The temporal resolution of near-infrared light intensity in behaviorally trained mice wearing soft contact lenses was determined based on behavioral data.

[0073] According to an embodiment of the present invention, by obtaining the behavioral data of mice distinguishing near-infrared light of multiple light intensities, the response of mice to near-infrared light stimulation can be quickly collected and analyzed, thereby improving the efficiency of the experiment and the accuracy of the data. It also illustrates that the soft corneal contact lens of the present invention can not only enable humans to have the ability to perceive near-infrared light, but also enable mice to have the ability to see near-infrared light after wearing it.

[0074] According to an embodiment of the present invention, the training method of behavioral training mice comprises:

[0075] Placing the mouse to be trained in a box having a first training area and a second training area, wherein a passage is provided between the first training area and the second training area for the mouse to be trained to move;

[0076] Visible light with different frequency patterns is applied to the first training area and the second training area respectively, wherein the visible light with different frequency patterns corresponds to different electric shock patterns one by one, so that the mice can learn the ability to distinguish visible light with different frequency patterns through the electric shock patterns, and the frequency pattern of visible light should be consistent with the frequency pattern of near-infrared light.

[0077] According to an embodiment of the present invention, non-invasive neural regulation is achieved by stimulating mice with electric shock and visible light, avoiding invasive brain implants and the brain tissue damage and physical restraint they bring, and can effectively train mice to respond to and distinguish light stimulation. This method combines behavioral training and neurophysiological testing to improve the accuracy and reliability of the test. The scheme configures a multi-mode visible light source to emit visible light signals of different modes to stimulate mice to produce different behavioral characteristics, so that the trained mice can make corresponding responses when seeing visible light signals, and then make corresponding responses when wearing soft corneal contact lenses that can convert near-infrared light into visible light, which can be used to prove that soft corneal contact lenses can convert near-infrared light into visible light that is visible to mice.

[0078] As an embodiment of another aspect of the present invention, there is provided a soft corneal contact lens, comprising:

[0079] Soft contact lenses including upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ and poly(2-hydroxyethyl methacrylate); wherein the upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ The mass concentration is 0.1%~10%.

[0080] According to an embodiment of the present invention, upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er3+ The mass concentration can be 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, but is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0081] According to an embodiment of the present invention, upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ With the ability to convert low-energy light such as near-infrared light into high-energy visible light, poly(2-hydroxyethyl methacrylate) (pHEMA) is a polymer that forms a hydrogel in water, has good biocompatibility and comfort, and is compatible with upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ Soft corneal contact lenses with similar refractive indices that combine upconversion nanoparticles and poly(2-hydroxyethyl methacrylate) can enhance the response to near-infrared light, thereby potentially improving the imaging quality in near-infrared imaging; poly(2-hydroxyethyl methacrylate) hydrogel has obvious temperature sensitivity, which enables the lens to adjust its shape and hardness according to changes in body temperature, thereby improving wearing comfort.

[0082] In some specific embodiments of the present invention, the refractive index matching method is used to determine the upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ Poly(2-hydroxyethyl methacrylate), a polymer material having a similar refractive index, is used as a solvent.

[0083] Specifically, the upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ The method comprises dissolving the poly(vinyl alcohol) in a zinc bromide solvent at different concentrations to obtain a plurality of test solutions; comparing the refractive index of the plurality of test solutions with a plurality of pure solvents, wherein the plurality of pure solvents include poly(methyl methacrylate), polydimethylsiloxane, silicone hydrogel-1, silicone hydrogel-2, poly(2-hydroxyethyl methacrylate)-1, poly(2-hydroxyethyl methacrylate)-2, poly(ethyl acetate) and polyamic acid; and determining the target solvent as poly(2-hydroxyethyl methacrylate) according to the comparison results.

[0084] Among them, silicone hydrogel-1 used 3-(methacryloyloxy)propyl(trimethylsiloxy)silane (TRIS) and polyethylene glycol (PEGMA) monomers, silicone hydrogel-2 used N,N-dimethylacrylamide (DMA) and 2-hydroxyethyl methacrylate (HEMA) monomers; poly(2-hydroxyethyl methacrylate)-1 used 2-hydroxyethyl methacrylate (HEMA), 2-hydroxy-2-methylpropenoate (photoinitiator), and ethylene glycol dimethacrylate (EGDMA), and poly(2-hydroxyethyl methacrylate)-2 used HEMA, EGDMA, and 2-hydroxy-2-methylpropenoate.

[0085] According to an embodiment of the present invention, a method for preparing a soft corneal contact lens comprises:

[0086] Upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ After being mixed with a monomer solution of poly(2-hydroxyethyl methacrylate), the soft corneal contact lens is prepared by mold curing.

[0087] According to an embodiment of the present invention, the up-conversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ After mixing with a monomer solution of poly(2-hydroxyethyl methacrylate), a soft corneal contact lens is prepared by a mold curing method. This preparation method has high production efficiency, is simple and fast, has low cost, and has good repeatability, and is suitable for large-scale production.

[0088] According to an embodiment of the present invention, upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ The preparation method comprises:

[0089] Upconversion nanoparticles NaGdF4: Yb 3+ ,Er 3+ Dispersed in water to obtain NaGdF4: Yb 3+ ,Er 3+ Aqueous solution;

[0090] In NaGdF4: Yb 3+ ,Er 3+ Add ligand chain polyvinyl pyrrolidone and chloroauric acid solution to the aqueous solution, stir and react, add reducing agent and centrifuge to obtain upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ .

[0091] According to the embodiments of the present invention, the upconversion luminescence performance can be enhanced by combining gold nanoparticles with upconversion nanoparticles. By introducing gold nanoparticles on the surface of upconversion nanoparticles, more functional groups can be further introduced through surface modification of gold nanoparticles, thereby expanding the application range of upconversion nanoparticles. By introducing a ligand chain polyvinylpyrrolidone (PVP) on the surface of upconversion nanoparticles, its water solubility can be improved and the biocompatibility of the nanoparticles can be improved, thereby reducing the potential toxicity to organisms.

[0092] The scheme of the present invention will be further explained below with reference to specific examples. Unless otherwise stated in the following examples, conventional commercial reagents are used.

[0093] In the following embodiments, the term "resolution coefficient" refers to the accuracy of resolution, which is calculated by subtracting the probability of random judgment correct events from the proportion of all correct ones. The expected accuracy of random judgment is (100 / n)%, where "n" represents the number of choices. The resolution coefficient calculation formula is (subject response accuracy - (100 / n)%) / (100% - (100 / n)%).

[0094] Example 1 Upconversion of gold nanoparticles Au / NaGdF4: Yb 3+ ,Er 3+ Synthesis

[0095] Synthesis of upconversion nanoparticles NaGdF4: Yb by high temperature thermal decomposition method 3+ ,Er 3+ , the upconversion nanoparticles NaGdF4: Yb 3+ ,Er 3+ Dispersed in deionized water, and added with 2 mL of 2.4 mM ligand chain polyvinylpyrrolidone (PVP) and 20 μL of 10 mM chloroauric acid solution, respectively.

[0096] After stirring at 25°C for 15 min, 900 μL of 100 mM ascorbic acid reducing agent was added and the reaction was stirred for 30 min. Au can be loaded on the surface of UCNPs.

[0097] The modified nanoparticles were then centrifuged and washed several times with deionized water (DI) to obtain purified upconversion gold nanoparticles Au / NaGdF4: Yb 3+ ,Er 3+ .

[0098] In order to enhance the dispersion of UCNPs in contact lenses and remove oleic acid molecules, a modification process was performed: First, 50 mg of up-converted UCNPs were dispersed in 10 ml of deionized water. Then 50 μL of 1 M HCl solution was added. The suspension was then magnetically stirred for 3 h, followed by multiple rounds of centrifugation and washing. The nanomorphology of UCNPs was observed using a field emission scanning electron microscope (SEM, Gemini 500, CarlZeiss Jena, Germany) at an accelerating voltage of 3 kV. The results are shown in Figure 2. Figure 2 shown.

[0099] Figure 2 This is a scanning electron microscope image of upconversion nano-gold particles according to an embodiment of the present invention.

[0100] According to Figure 2 It can be seen that upconversion nano-gold particles with uniform size and no agglomeration are synthesized by the preparation method of the present invention.

[0101] The infrared (IR) spectrum of oleic acid-free UCNPs in the full range of 1000 ~3500 cm-1 was characterized using a Nicolet 759 Fourier transform infrared (FT-IR) spectrometer. Figure 3 shown.

[0102] Figure 3 This is the Fourier transform infrared spectrum of the up-conversion nano-gold particles according to the embodiment of the present invention.

[0103] according to Figure 3 It can be seen that the upconversion gold nanoparticles prepared in Example 1 successfully removed the surface oleic acid molecule modification.

[0104] Example 2 Solvent Screening for Upconversion Nanoparticles

[0105] The refractive index of the nanoparticle colloidal solution was compared with the refractive index n of the corresponding pure solvent. The upconversion nanoparticles (UCNPs) without oleic acid were dispersed in zinc bromide solutions with different mass concentrations of 0.2682 g / mL, 0.6705 g / mL, 0.8940 g / mL, 1.1846 g / mL, and 1.5645 g / mL, and the corresponding refractive indices were 1.3725, 1.4195, 1.4440, 1.4874, and 1.5322, respectively.

[0106] Thus, a stable colloidal solution was formed, and the final nanoparticle mass fraction was 12%. Then, the refractive index of the colloidal solution and polymer at various mass concentrations was measured. The results are as follows: Figure 4 and Figure 5 shown.

[0107] Figure 4This is a graph showing the refractive index test results of upconversion nanoparticles at different mass concentrations according to an embodiment of the present invention; Figure 5 This is a result diagram of solvent screening by refractive index matching in an embodiment of the present invention; Figure 6 This is a comparison chart of the transparency of different solvents in the embodiments of the present invention.

[0108] according to Figure 4 , Figure 5 and Figure 6 It can be seen that, where n is the refractive index, 2-hydroxyethyl methacrylate has the closest refractive index to the upconversion nanoparticles. Therefore, when 2-hydroxyethyl methacrylate is used as a solvent for the upconversion nanoparticles, it has good light transmittance and transparency and will not affect the imaging of other visible light by the wearer.

[0109] Example 3 Synthesis of poly (2-hydroxyethyl methacrylate)

[0110] 0.085 g of ethylene glycol dimethacrylate was immersed in 4 mL of 2-hydroxyethyl methacrylate. Then, 3 mL of deionized water and 0.085 g of 2-hydroxy-2-methylpropenone were gradually added. Stirring was carried out in a dark environment for 30 minutes, and finally the monomer suspension was sealed to avoid visible light.

[0111] Example 4 Preparation of soft corneal contact lenses

[0112] Figure 7 The present invention is a flow chart of the preparation of soft corneal contact lenses according to an embodiment of the present invention.

[0113] Preparation process Figure 7 As shown, UCNPs were added to the monomer solution of Example 3 and subjected to ultrasonic treatment. They were then immersed in a silicon wafer or contact lens mold and irradiated with 365 nm UV light for 20 min to catalyze the reaction. The film or contact lens was further peeled off from the silicon wafer or mold and washed with DI water / ethanol solution at a volume ratio of 1:1 at 50°C for 10 h to remove unreacted monomers.

[0114] Figure 8 This is a diagram of a soft corneal contact lens prepared according to an embodiment of the present invention.

[0115] according to Figure 8 It can be seen that the preparation method of the present invention can be used to prepare soft corneal contact lenses with high light transmittance, clear imaging and no deformation.

[0116] Example 5 Perception Threshold Test of Mice Wearing Soft Contact Lenses: Pan-electroretinogram Response to Near-Infrared Light

[0117] The mice were anesthetized after wearing or not wearing soft corneal contact lenses, and 535nm visible light and 980nm near-infrared light were applied to the mice, and the mice were tested for full electroretinogram. The test results are shown in the figure. Fig. 9 shown.

[0118] Fig. 9 This is a comparison diagram of the full electroretinogram response of mice in the examples of the present invention to near-infrared light.

[0119] according to Fig. 9 It can be seen that mice wearing soft corneal contact lenses can respond to near-infrared light, while mice not wearing soft corneal contact lenses cannot respond to near-infrared light, and the ability of mice to respond to visible light is not affected after wearing the soft corneal contact lenses of the present invention.

[0120] Example 6 Perception threshold test of mice wearing soft contact lenses: detection of pupil light reflex ability to near-infrared light

[0121] A soft corneal contact lens was placed on one eye of the mouse, and near-infrared light of 980 nm was applied to observe the pupil contraction of both eyes of the mouse. The results are as follows: Fig.10 shown.

[0122] Fig.10 This is a graph showing the pupil light reflex ability test results of mice wearing soft corneal contact lenses according to an embodiment of the present invention.

[0123] according to Fig.10 It can be seen that the contralateral pupil of mice wearing soft contact lenses will shrink significantly after near-infrared light irradiation, while the pupil of mice not wearing soft contact lenses has no pupil light response after near-infrared light irradiation.

[0124] Example 7 Perception Threshold Test of Mice Wearing Soft Contact Lenses: Image Vision Pathway Detection of Near-Infrared Light

[0125] After the mice were anesthetized, they were stimulated with 980nm near-infrared light and 535nm visible light with or without a soft corneal contact lens placed on the lateral eye, and the field potentials of different areas of the cerebral visual cortex (V1) were recorded at the same time to reflect the activation of the mouse image visual pathway. The results are shown in Fig.11 The figure shows the statistical situation of the delay time of the visual cortical field potential after stimulation. The delay time is the interval between the light stimulation and the appearance of the visual cortical field potential. The data are mean ± SD, and the number of mice in each group for all experiments is 5. Two-tailed t-test, ns means no significant difference; *** means p < 0.001.

[0126] Fig.11This is a diagram showing the results of image visual pathway detection of near-infrared light in mice wearing soft corneal contact lenses according to an embodiment of the present invention.

[0127] according to Fig.11 It can be seen that the mice wearing soft corneal contact lenses have a cortical field potential response consistent with visible light after near-infrared light irradiation, while the mice not wearing the present invention have no response in the visual cortex after near-infrared light irradiation. It can be proved that soft corneal contact lenses can effectively convert 980nm near-infrared light into light visible to mice, thereby activating the mouse image visual pathway.

[0128] Example 8 Testing of near-infrared light temporal resolution in mice wearing soft contact lenses

[0129] The mice were placed in a behavior test box, which had two boxes connected by a partition in the middle, with a hole on the partition for the mice to pass through freely. Program-controlled 980nm LED light panels or 535nm LED light panels were placed on the walls of both boxes, and a program-controlled electric shock board was placed at the bottom of the box.

[0130] Conduct behavioral training on mice: link light of different frequencies to foot electric shock stimulation or no stimulation, give light signals of different frequencies to the two sides of the box, corresponding to foot electric shock stimulation or no stimulation respectively. After 20 seconds of light signal, give mice 5 seconds to react. After behavioral training, mice will quickly avoid the non-stimulation box according to the light frequency on both sides.

[0131] After the mice were trained with 535nm visible light stimulation, they could recognize and avoid electric shock stimulation according to the light frequency information. At this time, the mice were given the present invention, and the 535nm light signal was replaced with a 980nm light signal, while the original stimulation frequency was maintained. The results were as follows: Fig.12 As shown, the statistical target is the active avoidance success reaction time of the mouse, and the reaction time is from the moment of light stimulation to the moment when the mouse body completely avoids another box. The data are mean ± SD, and the number of mice in each group for all experiments is 5. Two-tailed t-test, ns means no significant difference; *** represents p < 0.001.

[0132] Fig.12 This is a diagram showing the results of image visual pathway detection of near-infrared light in mice wearing soft corneal contact lenses according to an embodiment of the present invention.

[0133] according to Fig.12 It can be seen that the mice wearing soft corneal contact lenses can make correct judgments and avoid electric shock stimulation, while the mice not wearing the soft corneal contact lenses of the present invention cannot recognize near-infrared information, and their ability to avoid electric shock stimulation is significantly lower than that of the experimental group mice.

[0134] Example 9 Testing of the Perception Threshold of Near-Infrared Light Intensity of the Person Under Test

[0135] The test subjects stared at a visible or near-infrared LED array panel with their dominant eye while wearing soft contact lenses or not wearing soft contact lenses, and the other eye was covered. At the same time, the test subjects' heads were stabilized and the viewing distance was kept fixed.

[0136] Visible light or near-infrared light with different light power intensities was designed to pass through a 535 nm or 980 nm LED light board to test the visual sensitivity of each person under test in a dark room and under an ambient light background of 100 lux.

[0137] The visual sensitivity test for each light power intensity included 20 trials, each trial consisted of two consecutive stimulations, namely, no flash followed by a 100-ms flash or a 100-ms flash followed by no flash. There was an auditory cue before each stimulation, and the subjects were asked to determine the order of the two paired stimuli.

[0138] Fig.13 This is a schematic diagram of a test of a near-infrared light intensity perception threshold of a person to be tested according to an embodiment of the present invention; Fig.14 This is a graph showing the test results of the perception threshold of near-infrared light intensity of a person under test according to an embodiment of the present invention.

[0139] according to Fig.13 and Fig.14 It can be seen that the test subjects wearing soft corneal contact lenses can detect near-infrared light in different environments and obtain near-infrared light perception curves close to the detection threshold by testing them with their eyes open and closed in a dark room and in a background light environment. By comparing the perception of near-infrared light by the test subjects wearing soft corneal contact lenses with their eyes open and closed, it can be found that in a bright field environment, the threshold of near-infrared light that can be detected by the test subjects wearing soft corneal contact lenses with their eyes closed is lower than that with their eyes open. This also shows that the near-infrared visual function achieved by wearing the present invention has higher penetration and can be applied to a variety of visual impairment scenarios.

[0140] Example 10: Test of the time resolution of near infrared light by the person under test

[0141] After wearing soft contact lenses, the test subjects were given near-infrared light and continuous light (>10 kHz) with specific flickering frequencies for testing. Each test consisted of 10 trials, and each trial included two consecutive stimuli, namely, continuous light (>10 kHz) followed by flickering light, or flickering light followed by continuous light (>10 kHz). Each stimulation lasted for 2 seconds, with a duty cycle of 50%.

[0142] Before each stimulus, there is an auditory cue, and the test subject is asked to determine the order of the two paired stimuli; if the test subject has the ability to distinguish the specific flickering frequency of near-infrared light, can distinguish the flickering light and the constant light and give the correct answer to the order of their stimuli, the test result is as follows: Fig.15 shown.

[0143] Fig.15 This is a graph showing the time resolution test results of near-infrared light for a person under test according to an embodiment of the present invention.

[0144] according to Fig.15 It can be seen that by counting the correct rate of the test subjects' answers, it can be seen that after wearing soft corneal contact lenses, the test subjects have a similar time frequency perception ability for near-infrared light as for visible light.

[0145] Example 11 Testing of the spatial resolution and information transmission ability of near-infrared light by the test subjects

[0146] Near-infrared light was used to encode the frequency and flashing duration of different information. The changes in stimulation frequency and flashing times corresponding to different letters were as follows: "a" - 2 flashes at 2HZ, "b" - 2 flashes at 5HZ, "c" - 3 flashes at 2HZ, "d" - 3 flashes at 5HZ, "e" - 4 flashes at 2HZ, and "f" - 4 flashes at 5HZ.

[0147] The ability of the tested persons to recognize different information is counted, and then the monitoring results of the tested persons' ability to transmit near-infrared light information are evaluated.

[0148] Fig.16 This is a graph showing the spatial resolution test results of near-infrared light for a person under test in an embodiment of the present invention.

[0149] According to Fig.16 It can be seen that the test subjects wearing soft contact lenses can well identify the information encoded by the near-infrared light in the test, while the test subjects not wearing soft contact lenses cannot obtain the near-infrared light information.

[0150] The above specific embodiments further illustrate the purpose, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above are only specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. Application of a soft corneal contact lens in infrared visual imaging detection, wherein: The soft corneal contact lens comprises up-conversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ and poly(2-hydroxyethyl methacrylate), the soft corneal contact lens being used to convert near-infrared light with a wavelength of 780 nm to 1100 nm into light visible to a subject to be tested; The infrared visual imaging detection method comprises: Determining the perception threshold of the object to be tested for the near-infrared light intensity by detecting the recognition reaction result of the object to be tested wearing the soft corneal contact lens to the near-infrared light; In the case where it is determined that the object to be tested responds to the near-infrared light according to the perception threshold of the object to be tested for the near-infrared light intensity, performing a near-infrared light time resolution test on the object to be tested to determine the time resolution identification information of the object to be tested for the near-infrared light; A detection result based on the soft corneal contact lens in infrared visual imaging is obtained according to the near-infrared light intensity perception threshold and the time resolution identification information.

2. The use according to claim 1, wherein: The step of determining the perception threshold of the object to be tested for the near-infrared light intensity by detecting the recognition reaction result of the object to be tested wearing the soft corneal contact lens to the near-infrared light comprises: Applying first near-infrared light stimulation of multiple light intensities to the object to be measured, wherein the first near-infrared light stimulation is applied in a preset mode; Detecting a response behavior of the object to be tested to the first near-infrared light stimulus to obtain a first response result; Matching the first response result with the preset pattern to determine a first matching result; The perception threshold of the object to be measured for the near-infrared light intensity is determined according to the plurality of first matching results corresponding to the first near-infrared light stimuli of the plurality of light intensities.

3. The use according to claim 1, wherein: The performing of a near-infrared light time resolution test on the object to be tested to determine the time resolution identification information of the object to be tested for near-infrared light comprises: Applying a second near-infrared light stimulus of multiple frequency modes to the object to be tested, wherein the frequency mode is a stroboscopic mode of a combination of continuous light and flashing light, or a stroboscopic mode of continuous light alone; Detecting a response behavior of the object to be tested to the second near-infrared light stimulus to obtain a second response result; Matching the second response result with the frequency pattern to determine a second matching result; The time resolution identification information of the object to be measured for the near-infrared light is determined according to the plurality of second matching results corresponding to the second near-infrared light stimuli of the plurality of frequency modes.

4. The use according to claim 1, wherein: When the object to be detected is a person to be detected, the infrared visual imaging detection method further includes: By testing the near-infrared light spatial resolution of the person to be tested, the spatial resolution identification information of the person to be tested for the near-infrared light is determined.

5. The use according to claim 4, wherein: The determining of the near-infrared light spatial resolution identification information of the person to be tested by testing the near-infrared light spatial resolution of the person to be tested comprises: Applying a third near-infrared light stimulus having a plurality of preset patterns to the persons to be tested respectively; Detecting the response behavior of the person to be tested to the third near-infrared light stimulation to obtain a third response result; Matching the third response result with the preset pattern to determine a third matching result; The spatial resolution identification information of the person to be tested for near-infrared light is determined according to the plurality of third matching results corresponding to the third near-infrared light stimulation of the plurality of preset patterns.

6. The use according to claim 1, wherein: In the case where the object to be tested is a mouse, the near-infrared light time resolution test is performed on the object to be tested to determine the time resolution identification information of the object to be tested for the near-infrared light, including: Placing a behavior-trained mouse wearing the soft corneal contact lens in a box having a first area and a second area, wherein a passage is provided between the first area and the second area for the mouse to move; and the behavior-trained mouse has the behavior ability to avoid visible light; Applying near-infrared light stimulation of multiple frequency modes to the first area or the second area; Obtaining behavioral data of the behaviorally trained mouse wearing the soft corneal contact lens to distinguish near-infrared light of multiple light intensities; The time resolution recognition information of the near-infrared light intensity of the behavior-trained mouse wearing the soft corneal contact lens is determined according to the behavior data.

7. The use according to claim 6, wherein: The training method of the behavioral training mice comprises: Placing the mouse to be trained in a box having a first training area and a second training area, wherein a passage is provided between the first training area and the second training area for the mouse to be trained to move; Visible light of different frequency patterns is applied to the first training area and the second training area respectively, wherein the visible light of different frequency patterns corresponds to different electric shock patterns one by one, so that the mice can learn the behavioral ability to distinguish visible light of different frequency patterns through the electric shock patterns.

8. A soft corneal contact lens, comprising: The soft corneal contact lens comprises up-conversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ and poly(2-hydroxyethyl methacrylate); wherein the upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ The mass concentration is 0.1%~10%.

9. The soft contact lens according to claim 8, wherein: The preparation method of the soft corneal contact lens comprises: The upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ After being mixed with poly (2-hydroxyethyl methacrylate), the soft corneal contact lens is prepared by mold curing.

10. The soft contact lens according to claim 9, wherein: The upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ The preparation method comprises: The upconversion nanoparticles NaGdF4: Yb 3+ ,Er 3+ Dispersed in water to obtain NaGdF4: Yb 3+ ,Er 3+ Aqueous solution; In the NaGdF4: Yb 3+ ,Er 3+ Add ligand chain polyvinyl pyrrolidone and chloroauric acid solution to the aqueous solution, stir and react, add reducing agent and centrifuge to obtain upconversion gold nanoparticles Au / NaGdF4:Yb 3+ ,Er 3+ .

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