A tear collection patch

Abstract

This invention provides a tear collection patch, comprising, from near to far from the eye, a biomimetic flexible substrate, a superhydrophilic drainage layer, a storage cavity, and a sealing cap. The superhydrophilic drainage layer includes a hydrophilic medical fiber membrane and a superhydrophilic coating. The hydrophilic medical fiber membrane is prepared by electrospinning medical hydrophilic fibers, and the superhydrophilic coating is formed by immersing the hydrophilic medical fiber membrane in a superhydrophilic coating solution and then curing it. The biomimetic flexible substrate has a biomimetic adhesive layer that automatically adheres to the target location. The superhydrophilic drainage layer absorbs tears into the storage cavity. This invention achieves instantaneous tear absorption and painless adhesion by designing a drainage layer with superhydrophilic properties and a biomimetic adhesive substrate working synergistically. The biomimetic adhesive substrate reduces the risk of corneal irritation, ensuring that the collected tears are in a normal physiological state rather than due to stress secretion, thus solving the problems of reliance on manual operation and low efficiency in traditional collection methods.

Description

Technical Field

[0001] This invention belongs to the field of tear collection and detection technology, and particularly relates to a tear collection patch. Background Technology

[0002] For modern people who bear an excessive burden on their eyes, eye health is an important factor in maintaining a healthy life.

[0003] In particular, tears are composed of inorganic electrolytes such as calcium and magnesium, as well as organic components such as glucose, lactic acid, proteins, and lipids, and therefore health status can be measured by analyzing the concentration and composition of tears.

[0004] Currently, the mainstream clinical techniques for collecting tears are capillary collection and filter paper adsorption. The capillary collection method involves gently touching the edge of the eyelid with a glass tube and relying on capillary action to absorb the tears. The filter paper adsorption method involves inserting a strip of filter paper into the conjunctival sac, absorbing the tears through the filter paper, and then cutting out a sample.

[0005] Therefore, existing clinical techniques for collecting tears have the following problems:

[0006] It relies heavily on manual operation: the contact angle and pressure between the capillary / filter paper and the ocular surface must be precisely controlled, and improper operation can easily lead to sample contamination or collection failure.

[0007] • Insufficient biocompatibility of materials: Rigid capillaries or filter paper fibers may irritate the cornea, causing reflexive tear secretion that interferes with test results;

[0008] • The collection time is relatively long: the test strip method causes obvious discomfort to the test subjects; it is easy to be contaminated during the collection process; at the same time, the test strip itself has a retention effect, which can cause abnormal lipid and some protein content; and the subsequent elution process is cumbersome.

[0009] Therefore, a rapid drainage solution is provided that does not rely on passive capillary action or manual operation and is applicable to situations with low tear secretion. Summary of the Invention

[0010] To address the above problems, this invention provides a tear collection patch that not only reduces reliance on manual operation but also improves material biocompatibility and shortens collection time.

[0011] To achieve the above objectives, the technical solution of the present invention is as follows:

[0012] A tear collection patch, comprising, from near to far from the eye, a biomimetic flexible substrate, a superhydrophilic drainage layer, a storage cavity, and a sealing cap;

[0013] The superhydrophilic flow-guiding layer includes a hydrophilic medical fiber membrane and a superhydrophilic coating. The hydrophilic medical fiber membrane is prepared by electrospinning of medical hydrophilic fibers, and the superhydrophilic coating is formed by immersing the hydrophilic medical fiber membrane in a superhydrophilic coating solution and then curing it.

[0014] The biomimetic flexible substrate has a biomimetic adhesion layer, which automatically adheres to the target position, and the superhydrophilic drainage layer absorbs tears into the storage cavity.

[0015] The sealing cap seals the storage cavity, and the sealing cap is detachably connected to the storage cavity.

[0016] In a preferred embodiment of the present invention, a one-way anti-backflow valve is further included. The one-way anti-backflow valve is disposed between the superhydrophilic guide layer and the storage cavity. The one-way anti-backflow valve is configured to allow tear fluid to flow into the storage cavity in one direction only, preventing backflow to the superhydrophilic coating.

[0017] In a preferred embodiment of the present invention, the one-way anti-backflow valve includes an inlet end and an outlet end, the outlet end being deformable under tear pressure to open or close; the inlet end is attached to the superhydrophilic flow guiding layer, and the outlet end is located in the storage cavity.

[0018] In a preferred embodiment of the present invention, the liquid outlet is a funnel-shaped structure.

[0019] In a preferred embodiment of the present invention, the opening and closing pressure of the liquid outlet is less than or equal to 0.1 kPa.

[0020] In a preferred embodiment of the present invention, the medical hydrophilic fiber is selected from any one or more of the following: cotton fiber, chitosan fiber, alginate fiber, polyvinyl alcohol fiber, polyacrylic acid fiber, polyethylene glycol modified fiber, polyurethane hydrophilic fiber, collagen fiber, or silk fibroin fiber.

[0021] The superhydrophilic coating is a polyvinyl alcohol coating or a graphene hydrophilic coating.

[0022] In a preferred embodiment of the present invention, the biomimetic adhesion layer is a dopamine adhesion layer or a polydopamine-chitosan adhesion layer.

[0023] In a preferred embodiment of the present invention, the thickness of the biomimetic flexible substrate is 0.2-1 mm, and the thickness of the biomimetic adhesion layer is 50-100 nm.

[0024] In a preferred embodiment of the present invention, a sampling port is provided on the storage cavity.

[0025] In a preferred embodiment of the present invention, the inner wall of the storage cavity is coated with a pH-sensitive color-changing material.

[0026] In a preferred embodiment of the present invention, the central region of the tear collection patch has a hollowed-out area.

[0027] In a preferred embodiment of the present invention, the edge of the hollowed-out area has an annular transition zone, wherein the annular transition zone gradually thins out at the edge of the hollowed-out area.

[0028] In a preferred embodiment of the present invention, the cross-section of the hollowed-out area is circular or elliptical, the diameter of the circle is 3-5mm, the major axis of the ellipse is 4mm, and the minor axis is 3mm.

[0029] Because the present invention adopts the above technical solution, it has the following advantages and positive effects compared with the prior art:

[0030] The tear collection patch provided by this invention has a biomimetic flexible substrate, a superhydrophilic drainage layer, a storage cavity, and a sealing cap. The biomimetic flexible substrate has a biomimetic adhesive layer that can automatically adhere to the lower eyelid conjunctiva and maintain a stable bond. The superhydrophilic drainage layer includes a hydrophilic medical fiber membrane and a superhydrophilic coating. The hydrophilic medical fiber membrane is made of medical hydrophilic fibers woven electrostatically, thus possessing numerous micropores that can rapidly absorb and conduct tears. The surface of the hydrophilic medical fiber membrane has a hydrophilic coating, which is bonded through physical adsorption or chemical grafting, significantly reducing the surface water contact angle, allowing tears to spread rapidly and be guided along the fiber network. Therefore, this application, due to its biomimetic flexible substrate, can automatically adhere to the target location, achieving automatic adsorption and positioning, thereby reducing reliance on manual operation; it also improves the biocompatibility of the material, reduces the risk of corneal irritation, and ensures that the collected tears are in a normal physiological state rather than under stress; and the use of a superhydrophilic drainage layer accelerates tear adsorption, shortening the collection time. Attached Figure Description

[0031] Figure 1 This is a schematic diagram of a tear collection patch according to an embodiment of the present invention;

[0032] Figure 2 This is a schematic diagram of the structure of the one-way anti-backflow valve according to an embodiment of the present invention;

[0033] Explanation of reference numerals in the attached drawings: 1-Bionic flexible substrate; 101-Bionic adhesion layer; 102-Medical silicone substrate; 2-Superhydrophilic flow guiding layer; 3-One-way anti-backflow valve; 301-Inlet end; 302-Outlet end; 4-Storage chamber; 5-Sealing cap; 6-Hollowed-out area. Detailed Implementation

[0034] Current tear collection technologies suffer from the following main technical drawbacks: traditional capillary collection methods require precise control of the contact angle and pressure between the capillary and the ocular surface, and improper operation can easily lead to sample contamination; the materials used in filter paper adsorption methods may irritate the cornea, triggering reflexive tear secretion and interfering with test results; and the collection process often takes more than 30 seconds, resulting in low patient cooperation. The root cause of these problems lies in the fact that current technologies rely on passive capillary action and manual operation, failing to address the issue of rapid drainage under low tear secretion conditions, and the material interface design is not optimized for tear-device interaction.

[0035] To address the problems of existing tear collection technologies, such as high dependence on manual operation, insufficient biocompatibility of materials, and excessively long collection times, this invention proposes an innovative solution through a combination of bionics and materials science. The core concept of this invention lies in the synergistic effect of a nanostructured guide layer with superhydrophilic properties and a biomimetic adhesive substrate, achieving instantaneous tear adsorption and painless adhesion. The biomimetic adhesive substrate reduces the risk of corneal irritation, ensuring that the collected tears are in a normal physiological state rather than due to stress. This design solves the problems of reliance on manual operation and low efficiency in traditional collection methods.

[0036] The tear collection patch of the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. The advantages and features of the present invention will become clearer from the following description.

[0037] See Figure 1 A tear collection patch, comprising, from near to far from the eye, a biomimetic flexible substrate 1, a superhydrophilic drainage layer 2, a storage cavity 4, and a sealing cap 5. The sealing cap 5 seals the storage cavity 4, and the sealing cap 5 and the storage cavity 4 are detachably connected, for example by a snap-fit ​​connection. When in use, the sealing cap 5 is fastened onto the storage cavity 4 to seal the storage cavity 4 and prevent tear sample contamination and evaporation.

[0038] The superhydrophilic flow-guiding layer 2 comprises a hydrophilic medical fiber membrane and a superhydrophilic coating. The hydrophilic medical fiber membrane is made from medical hydrophilic fibers, such as cotton fibers, chitosan fibers, alginate fibers, polyvinyl alcohol fibers, polyacrylic acid fibers, polyethylene glycol modified fibers, polyurethane hydrophilic fibers, collagen fibers, or silk fibroin fibers, or any one or more of these. The medical hydrophilic fibers are prepared using electrospinning technology to create the hydrophilic medical fiber membrane. The superhydrophilic coating can be prepared using the following methods: cleaning and drying the hydrophilic medical fiber membrane to remove surface impurities and ensure uniform coating adhesion; then preparing a hydrophilic coating solution, such as polyvinyl alcohol dissolved in pure water at a concentration of 1-5 wt% (graphene hydrophilic coating solution is also acceptable); immersing the hydrophilic medical fiber membrane in the hydrophilic coating solution to ensure uniform coating coverage of the fiber membrane surface while preventing clogging of the pore structure between fibers; removing the immersed fiber membrane and drying it at room temperature or in a low-temperature oven to allow the coating to cure and adhere to the fiber membrane surface. Hydrophilic medical fiber membranes have a large number of tiny pores, which can rapidly absorb and conduct tears. The flow-guiding layer on the hydrophilic medical fiber membrane has good hydrophilicity, and the contact angle can usually be less than 10°, which can enable the rapid spread of tears and their flow along the fiber network.

[0039] The biomimetic flexible substrate 1 includes a medical-grade silicone substrate 102 and a biomimetic adhesive layer 101. This biomimetic adhesive layer 101 is either a dopamine adhesive layer or an adhesive layer made of polydopamine-chitosan composite material. The polydopamine-chitosan composite material adhesive layer exhibits better water resistance. The biomimetic adhesive layer 101 mimics the adhesion mechanism of mussel byssal proteins, providing ≥10 N / m... 2 It possesses strong adhesion, enabling automatic adsorption and positioning; simultaneously, it exhibits excellent biocompatibility, reducing the risk of corneal irritation and ensuring that the collected tears are from a normal physiological state rather than stress-induced secretion. One method for preparing the biomimetic flexible substrate 1 includes: selecting medical-grade silicone as the substrate material, such as a dimethylsilane polymer with a Shore A hardness of 30±2; typically, the silicone precursor and crosslinking agent are mixed at a weight ratio of 10:1, and after vacuum degassing, the mixture is injected into a mold and cured at 80°C for 2 hours; the cured silicone substrate is then subjected to plasma surface activation (100W power, 30 seconds) to obtain a medical silicone substrate 102 with a thickness of 0.2-1mm, for example, 0.2, 0.5, 0.8, or 1mm; and then a biomimetic adhesion layer 101 is deposited on its surface using a sputtering method. The specific sputtering parameters for the dopamine biomimetic adhesion layer 101 are as follows: using dopamine hydrochloride as the target material, in a 10 mTorr argon atmosphere, the power is set to 50 W, and the sputtering time is 5 minutes, forming a dopamine biomimetic adhesion layer 101 with a thickness of approximately 50-100 nm, such as 50, 60, 70, 80, 90, and 100 nm. This dopamine layer simulates the adhesion mechanism of mussel byssal proteins, providing ≥10 N / m2 It has strong adhesion and excellent biocompatibility.

[0040] In this embodiment, the tear collection patch has a biomimetic adhesive layer 101 on a biomimetic flexible substrate 1 that automatically and stably adheres to the eyelid conjunctiva, and a super-hydrophilic drainage layer 2 that rapidly absorbs tears and guides them to the storage cavity 4.

[0041] In one preferred embodiment, the tear collection patch further includes a one-way anti-backflow valve 3, which is disposed between the superhydrophilic guide layer 2 and the storage cavity 4. The one-way anti-backflow valve 3 is configured to allow tear fluid to flow into the storage cavity 4 in one direction, preventing backflow to the superhydrophilic coating, which ensures the purity and integrity of the tear sample.

[0042] More preferably, the one-way anti-backflow valve 3 includes an inlet end 301 and an outlet end 302. The outlet end 302 can deform under the pressure of tear fluid to open or close. The inlet end 301 is attached to the superhydrophilic flow guide layer 2, and the outlet end 302 is located in the storage cavity 4. The opening and closing pressure of the outlet end 302 is less than or equal to 0.1 kPa. When the tear fluid in the storage cavity 4 flows from the outlet end 302 toward the inlet end 301, the outlet end 302 can deform and close under the pressure of tear fluid. At this time, the one-way anti-backflow valve is in a closed state.

[0043] The aforementioned one-way anti-backflow valve 3 uses the outlet end 302, which can undergo elastic deformation under pressure, to control the flow direction of tears. When the tears in the storage chamber 4 flow in the reverse direction to the outlet end 302, the outlet end 302 can deform and close under the action of tear pressure, thereby controlling the one-way anti-backflow valve 3 to be in a closed state; conversely, the outlet end 302 can open under the impact of tears, thereby controlling the one-way anti-backflow valve 3 to be in an open state.

[0044] It should be noted that since the outlet end 302 of the one-way anti-backflow valve 3 can deform under pressure, this means that the one-way anti-backflow valve 3 is made of a material that can produce elastic deformation, such as silicone.

[0045] To facilitate the control of the on / off state of the liquid outlet 302 of the one-way anti-backflow valve 3, in this embodiment, the liquid outlet 302 has a funnel-shaped structure, more specifically a "duckbill" shaped structure design, made of polydimethylsiloxane (PDMS) film with a thickness of 0.02-0.08mm, formed by soft photolithography, with an opening and closing pressure ≤0.1kPa, ensuring that the tear fluid can flow into the storage cavity 4 in one direction without backflow; this design ensures the purity and integrity of the tear fluid sample.

[0046] In a preferred embodiment, the storage cavity 4 is molded from medical-grade silicone, with a solvent of 5 μL. Its inner wall is coated with a pH-sensitive color-changing material, such as bromocresol purple, which appears blue when the tear pH is within the normal range of 6.4-7.7. Coating the storage cavity 4 with this pH-sensitive color-changing material confirms successful tear collection; successful collection is confirmed only when the material changes from pale yellow to purplish-red.

[0047] More preferably, a sampling port is provided on the storage cavity 4, and a micropipette can be used to extract tear samples from the sampling port. Preferably, the sampling port is located at the bottom edge of the storage cavity 4 for easy operation.

[0048] In some embodiments, the tear collection patch has a hollowed-out area 6 in the central region. The hollowed-out area 6 is designed to prevent the tear collection patch from compressing the ocular surface structure, ensuring that the natural tear secretion channel is not interfered with, and reducing eye discomfort caused by local pressure.

[0049] To further reduce local pressure, the edge of the hollowed-out area 6 has an annular transition zone, which is a region with a radial diameter of 1-2 mm, and the thickness gradually decreases from the edge of the hollowed-out area 6.

[0050] To accommodate different individuals' eye anatomical structures or better match the shape of the punctum region, the cross-section of the hollowed-out area 6 is circular or elliptical. The circular hollowed-out area 6 can be adjusted to different diameters within the range of 3-5mm, while the elliptical hollowed-out area 6 has a major axis of 4mm and a minor axis of 3mm to better match the shape of the punctum region.

[0051] In summary, the tear collection patch provided in this embodiment has the following technical effects:

[0052] 1. High-precision sample collection: The biomimetic adhesion layer 101 ensures stable adhesion between the patch and the conjunctiva of the eyelid, avoiding collection failure caused by displacement; the super-hydrophilic drainage layer 2 achieves instantaneous tear spread through a contact angle of less than 10°, improving collection efficiency; the one-way anti-backflow valve 3 prevents tear sample backflow, ensuring that the collected tears are all freshly secreted basal tears (avoiding reflection tear contamination).

[0053] 2. Biocompatibility and safety: The medical silicone substrate 102 matches the modulus of the eyeball, and the design of the avoidance hollow area 6 reduces the discomfort of wearing it; the biomimetic adhesive layer replaces chemical glue with biomimetic adhesion, eliminating the risk of allergies caused by traditional adhesives.

[0054] 3. Sample preservation reliability: The pH-sensitive color-changing storage chamber enables immediate judgment of sample validity.

[0055] The method of using the tear collection patch in this embodiment is as follows:

[0056] 1. Preparation before use: Before use, check the integrity of the patch packaging, open the sterile packaging, take out the patch, and avoid touching the surface of the patch's distribution layer with your fingers.

[0057] 2. Patch Placement: The subject remains seated and gently pulls down the lower eyelid. The patch is then lightly applied to the skin on the outer side of the lower eyelid conjunctival sac (about 1-2 mm from the eyelid margin). The biomimetic adhesive layer 101 is used to achieve automatic adhesion, ensuring that the central hollow area 6 is aligned with the lacrimal punctum to avoid compressing the ocular surface structure.

[0058] 3. Tear Collection: After the patch is placed, tears are rapidly drawn into the storage chamber 4 through the superhydrophilic guide layer 2, and the entire process is completed within 10 seconds. Successful collection can be confirmed by observing the color change of the pH-sensitive color-changing material in the storage chamber 4 (from pale yellow to purplish-red).

[0059] 4. Sample Retrieval: After collection, remove the patch and send the entire sealed sample directly for testing, or use a micropipette to extract the tear sample from the sampling port.

[0060] The tear collection patch in this embodiment standardizes tear sample collection, provides high-quality samples for tear testing of eye diseases, and promotes the popularization of precision medicine. At the same time, the collection process does not require professional medical personnel, which can reduce the burden on outpatient clinics and reduce the pressure on medical resources, thus having far-reaching social benefits.

[0061] The embodiments of the present invention have been described in detail above with reference to the accompanying drawings, but the present invention is not limited to the above embodiments. Even if various changes are made to the present invention, if these changes fall within the scope of the claims of the present invention and their equivalents, they shall still fall within the protection scope of the present invention.

Claims

1. A tear collection patch, characterized in that, From closest to furthest from the eye, the components include a biomimetic flexible substrate, a super-hydrophilic flow layer, a storage cavity, and a sealing cap. The superhydrophilic flow-guiding layer includes a hydrophilic medical fiber membrane and a superhydrophilic coating. The hydrophilic medical fiber membrane is prepared by electrospinning of medical hydrophilic fibers, and the superhydrophilic coating is formed by immersing the hydrophilic medical fiber membrane in a superhydrophilic coating solution and then curing it. The biomimetic flexible substrate has a biomimetic adhesion layer, which automatically adheres to the target position, and the superhydrophilic drainage layer absorbs tears into the storage cavity. The sealing cap seals the storage cavity, and the sealing cap is detachably connected to the storage cavity.

2. The tear collection patch according to claim 1, characterized in that, It also includes a one-way anti-backflow valve, which is disposed between the superhydrophilic guide layer and the storage cavity. The one-way anti-backflow valve is configured to allow tear fluid to flow into the storage cavity in one direction only, preventing backflow to the superhydrophilic coating.

3. The tear collection patch according to claim 2, characterized in that, The one-way anti-backflow valve includes an inlet end and an outlet end. The outlet end can deform under tear pressure to open or close. The inlet end is attached to the superhydrophilic flow guide layer, and the outlet end is located in the storage cavity.

4. The tear collection patch according to claim 3, characterized in that, The liquid outlet has a funnel-shaped structure.

5. The tear collection patch according to claim 3 or 4, characterized in that, The opening and closing pressure of the liquid outlet is less than or equal to 0.1 kPa.

6. The tear collection patch according to claim 1, characterized in that, The medical hydrophilic fiber is made of any one or more of the following: cotton fiber, chitosan fiber, alginate fiber, polyvinyl alcohol fiber, polyacrylic acid fiber, polyethylene glycol modified fiber, polyurethane hydrophilic fiber, collagen fiber, or silk fibroin fiber. The superhydrophilic coating is a polyvinyl alcohol coating or a graphene hydrophilic coating.

7. The tear collection patch according to claim 1, characterized in that, The biomimetic adhesion layer is a dopamine adhesion layer or a polydopamine-chitosan adhesion layer.

8. The tear collection patch according to claim 1 or 7, characterized in that, The thickness of the biomimetic flexible substrate is 0.2-1 mm, and the thickness of the biomimetic adhesion layer is 50-100 nm.

9. The tear collection patch according to claim 1, characterized in that, A sampling port is provided on the storage cavity.

10. The tear collection patch according to claim 1, characterized in that, The inner wall of the storage chamber is coated with a pH-sensitive color-changing material.

11. The tear collection patch according to claim 1, characterized in that, The tear collection patch has a hollowed-out area in its center.

12. The tear collection patch according to claim 11, characterized in that, The hollowed-out area has an annular transition zone at its edge, where the annular transition zone gradually thins out at the edge of the hollowed-out area.

13. The tear collection patch according to claim 11, characterized in that, The cross-section of the hollowed-out area is circular or elliptical, with the diameter of the circle being 3-5mm and the major axis of the ellipse being 4mm and the minor axis being 3mm.

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