Smart contact lens for collecting intraocular pressure and ocular surface temperature and its preparation method

Abstract

This invention belongs to the field of medical device technology, specifically a smart contact lens for collecting intraocular pressure and ocular surface temperature, and its preparation method. The smart contact lens of this invention includes an intraocular pressure sensor and a temperature sensor; both are ring-shaped and located on the same type of ocular surface. The intraocular pressure sensor consists of a sensing element and a gold electrode; the sensing element is a single-crystal silicon thin film; the temperature sensor consists of two rings of double-stranded serpentine gold electrodes; a polyimide film is used as the lower encapsulation layer to connect the temperature sensor and the intraocular pressure sensor, maintaining the overall stability of the device; the sensor layer and the encapsulation layer are encapsulated in upper and lower spherical encapsulation layers to form a contact lens. This smart contact lens can be worn on the cornea of ​​animals or humans without affecting the visual axis area, and can simultaneously monitor intraocular pressure and ocular surface temperature, exhibiting higher sensitivity, better repeatability, linearity, and good biocompatibility. It is mainly used for the screening, diagnosis, and prognostic monitoring of glaucoma.

Description

Technical Field

[0001] This invention belongs to the field of medical device technology, specifically relating to a wearable smart contact lens for collecting intraocular pressure and ocular surface temperature, and its preparation method. Background Technology

[0002] Smart contact lenses (SCLs) are representative of wearable ophthalmic health monitoring devices. They are composed of various sensors and a contact lens. At the forefront of international scientific research, they can monitor tear film composition, intraocular pressure, and integrate multiple therapeutic functions. Among these functions, intraocular pressure monitoring is the earliest developed and most maturely researched.

[0003] Research on intraocular pressure (IOP) monitoring stems primarily from the challenges in diagnosing and treating glaucoma. Glaucoma patients typically present with elevated intraocular pressure and, in later stages, optic nerve atrophy. This is a preventable but irreversible blinding eye disease once atrophy occurs. Normal IOP ranges from 10 to 21 mmHg; however, it fluctuates and exhibits diurnal rhythms. Traditional clinical IOP measurement methods, including the Goldmann tonometer, non-contact jet tonometer, and contact handheld tonometer, all rely on medical personnel for operation and provide a single reading per operation. This may lead to missed diagnoses or difficulty in assessing the effectiveness of glaucoma treatment. The prevalence of glaucoma in my country is as high as 2.58%, with two-thirds of glaucoma patients already in the middle or late stages at initial diagnosis. These limitations make glaucoma screening, diagnosis, treatment, and monitoring difficult.

[0004] Internationally, research reports on corneal contact lenses capable of real-time, long-term monitoring of intraocular pressure emerged in 2004. By 2016, Triggerfish, a product developed by the Swiss company SENSIMED for monitoring intraocular pressure in glaucoma patients, was officially approved by the FDA for clinical use. In contrast, the first domestic research on smart corneal contact lenses was published in 2013, 10 years later than the international level. Although Chinese scholars have reported more than 20 research results since 2019, there is still no SCL in my country that can achieve clinical application for a specific signal in the eye.

[0005] Currently, smart contact lenses can be categorized by their operating principles into piezoresistive, inductively coupled telemetry, microfluidic, and photonic crystal sensors. Piezoresistive sensors primarily consist of a sensing element whose resistance changes with geometric deformation. The latest intraocular pressure sensor based on the piezoresistive principle mainly uses graphene as its sensing material. While it boasts a high strain factor, it still suffers from several drawbacks: ocular toxicity, poor repeatability, and inability to scale up. Single-crystal silicon thin films are widely used in brain-computer interfaces, offering numerous advantages such as biocompatibility, good repeatability, and scalability; however, their application in intraocular pressure sensors in China remains unexplored.

[0006] In existing technologies, most smart contact lenses only achieve single-function signal acquisition, such as intraocular pressure monitoring, tear ion detection, and tear inflammatory factor detection. Due to the small area of ​​smart contact lenses (10~12mm in diameter) and the high difficulty of flexible integrated circuit technology, there is still little research on multifunctional smart contact lenses.

[0007] Changes in ocular surface temperature can explain the stages of corneal injury healing and are associated with corneal inflammation, serving as an important physical signal for the eye. Studies have shown that these changes are related to the occurrence and progression of various eye diseases (such as glaucoma, dry eye, diabetic retinopathy, pterygium, and scleritis). Currently, infrared imaging is the "gold standard" for measuring ocular surface temperature. However, some problems remain in practical applications: heat transfer from nearby tissues affects measurement results, and it is easily affected by blinking. Of particular note is that in real-world scenarios, such as assessing the real-time impact of eye protection devices on the ocular surface (with objects obstructing the view around the eye), infrared measurements are difficult to perform when wearing goggles.

[0008] Based on the above background, this invention aims to construct a dual-function smart contact lens that integrates intraocular pressure and ocular surface temperature monitoring. The intraocular pressure function is realized based on a single-crystal silicon thin film, and the ocular surface temperature function is realized based on a gold thin film. The entire device is manufactured through circuit design, micro-nano fabrication, and contact lens transfer, ultimately realizing the manufacturing of a dual-function smart corneal contact lens. Summary of the Invention

[0009] The purpose of this invention is to provide a wearable smart contact lens that integrates intraocular pressure and ocular surface temperature sensing and monitoring, which has high sensitivity and good biocompatibility, and a method for its preparation.

[0010] The smart contact lens provided by this invention mainly includes an intraocular pressure sensor and a temperature sensor; both are annular in shape and located on the same spherical surface (similar to the surface of an eye); wherein: The intraocular pressure sensor, located on the outer layer, consists of a sensing element and a gold electrode; the sensing element is a single-crystal silicon thin film. The temperature sensor is located in the inner layer and consists of two rings of double-stranded serpentine gold electrodes. A polyimide film is used as the lower coating layer, which has numerous radial serpentine connectors to connect the temperature sensor and the intraocular pressure sensor, maintaining the overall stability of the device. The enlarged circular ends of the intraocular pressure sensor and temperature sensor are the areas where silver paste and silver wire are fixed. The sensor layer and the lower covering layer are encapsulated within two upper and lower spherical encapsulation layers, forming a contact lens. (See also...) Figure 1 As shown.

[0011] in: In a circular intraocular pressure sensor, the radius of the ring is 4-6 mm, the thickness of the single-crystal silicon thin film is 500-550 nm, the linewidth is 75-150 μm, and its curvature can be customized, for example, 0.22 mm. -1 (Different definitions of curvature result in different sensitivities and measurement ranges); gold electrode thickness 150~200nm; linewidth greater than or equal to silicon thin film linewidth (75~150um), curvature >3mm -1 ; In a ring-shaped temperature sensor, the ring radius is 2-4 mm, the gold electrode thickness is 150-200 nm, the linewidth is 75-150 μm, and its curvature is >3 mm. -1 ; The lower layer is coated with a polyimide film with a thickness of 1.5~2.5um and a linewidth of 100um~200um.

[0012] The upper encapsulation layer is a PDMS and pHEMA hybrid layer with a thickness of 50~250um, and the upper encapsulation layer is a PDMS layer with a thickness of 50~250um.

[0013] Based on the design of a wearable smart contact lens, the contact lens consists of a PDMS layer (bottom layer) and a PDMS / pHEMA hybrid layer (top layer), with a sensor layer and a polyimide layer built into the contact lens. During fabrication, a large-scale single-crystal silicon thin film is transferred onto the polyimide layer using a stamping method. The pattern of the single-crystal silicon thin film is defined using ultraviolet lithography and reactive ion etching techniques. A gold target is sputtered using magnetron sputtering, and the gold thin film electrodes are defined using ultraviolet lithography and wet etching techniques. The entire pattern is then encapsulated using ultraviolet lithography and reactive ion etching techniques. The device is transferred to the PDMS layer (bottom layer) using a water-soluble adhesive tape method, and silver paste and silver wires are used for connection. After connection, the PDMS / pHEMA hybrid layer (top layer) is used for upper layer encapsulation.

[0014] The intelligent contact lens of the present invention can be worn on the cornea of ​​animals or humans without affecting the visual axis area. It can simultaneously monitor intraocular pressure and ocular surface temperature, and is mainly used for screening, diagnosis and prognosis monitoring of glaucoma. When worn, the sensing element in the intelligent corneal contact lens can sense the corneal changes and ocular surface temperature changes caused by intraocular pressure. By changing the resistance of the element, the output current changes. The two monitoring functions do not interfere with each other, and finally achieve linear synchronization between electrical and physical signals. The application of the present invention can optimize the current intelligent corneal lens (including: intraocular pressure sensor) in the following aspects: (1) It provides a circuit design scheme for a dual-function intelligent corneal lens that can simultaneously monitor intraocular pressure and ocular surface temperature; (2) It provides a new material and preparation scheme for intraocular pressure sensing, and the detection results show that it has higher sensitivity, better repeatability, linearity and good biocompatibility.

[0015] In practical applications, the wearable smart contact lens of this invention can be tested simply by connecting a silver wire to an electrochemical workstation.

[0016] For intraocular pressure monitoring, the sensitivity reaches 0.03% mmHg. -1 The linearity reaches 0.9896; the intraocular pressure sensor is almost unaffected by the temperature sensor; For temperature monitoring, the resistance change is 1.1Ω / ℃ within the range of 30-50℃, the temperature sensitivity coefficient is 0.3512, and the effect of small strain on the temperature sensor is negligible.

[0017] The above effects can help glaucoma patients or glaucoma animal models accurately monitor intraocular pressure fluctuations and changes in ocular surface temperature within the range of 10-50 mmHg, which can be used for screening, diagnosis, and prognosis monitoring.

[0018] The main innovations of this invention are: (1) Using single-crystal silicon thin film material, through single-crystal silicon thin film transfer technology, and using micro-nano process to define silicon thin film pattern in a personalized way, a high-sensitivity, high-measurement-range intraocular pressure sensor can be fabricated and personalized. (2) An innovative circuit integrating an intraocular pressure sensor and a temperature sensor was designed to integrate the two functional devices into the contact lens without affecting the visual quality after wearing it. (3) The connection method of silver paste and silver wire is used to realize wired active connection, which is more stable and simpler to manufacture than wireless passive signal; (4) The device surface is encapsulated with a mixture of PDMS and pHEMA to reduce friction and the impact of factors such as blinking on device performance. Attached Figure Description

[0019] Figure 1 This is a structural diagram of the smart contact mirror of the present invention.

[0020] Figure 2 This is a schematic diagram of the design of the intraocular pressure and temperature sensor of the present invention.

[0021] Figure 3 This is a flowchart illustrating the manufacturing process of the present invention.

[0022] Figure 4 This is a schematic diagram showing the connection of the present invention with silver paste and silver wire during application.

[0023] Figures 5-6 The figures show the experimental verification results of the intraocular pressure sensor and temperature sensor in this invention during application.

[0024] Figure 7 The figure shows the experimental verification results of the intraocular pressure sensor of the present invention, which is not affected by temperature.

[0025] In the diagram, the labels are as follows: 1 is the upper contact lens encapsulation layer; 2 is the lower contact lens encapsulation layer; 3 is the polyimide layer; 4 is the intraocular pressure (IOP) and temperature sensor layer; 5 is the IOP sensing element; 6 is the IOP sensing gold electrode; 7 is the temperature sensing gold electrode; 8 is the polyimide film; 9 is the circular bulge at the end of the IOP sensor (where the silver paste connects to the silver wire); 10 is the bulge at the end of the temperature sensor (where the silver paste connects to the silver wire); 11 is the silver paste; and 12 is the silver wire. Detailed Implementation

[0026] The method for manufacturing the wearable smart contact lens of the present invention is described in [reference needed]. Figure 3 As shown, the specific operation steps are as follows: (1) Spin coating and photolithography: Prepare a glass slide, spin-coat PMMA to prepare an adhesion layer with a thickness of about 1.2 μm, and heat it; dilute polyimide (PI) to 2.5:1 and spin-coat to prepare a PI film with a thickness of about 2.2 μm; (2) Transfer of silicon film: Prepare P-type silicon wafers, perform hydrofluoric acid pretreatment, and use the stamping method to transfer the single crystal silicon film onto the PI film; (3) Define the intraocular pressure sensing element: Define the silicon thin film according to the design pattern using ultraviolet lithography and reactive ion etching technology; (4) Define the electrodes of the intraocular pressure sensing element and the temperature sensor: Sputter chromium and gold targets using magnetron sputtering, and define the electrode pattern using ultraviolet lithography and wet etching techniques; (5) Overlaying the polyimide layer: Using ultraviolet lithography and reactive ion etching, the device overlay is completed according to the designed pattern; (6) Smart contact lens assembly: The finished device is immersed in acetone solution for 10 hours, and then transferred to the PDMS contact lens formed by the mold using the water-soluble adhesive tape method. Silver glue and silver wire are used for wire connection, and the upper device is encapsulated using a PDMS and pHEMA mixed solution (5:1).

[0027] Figure 1 This is a schematic diagram of the structure of the smart contact lens of the present invention. The upper contact lens encapsulation layer 1 is composed of a 10:1 mixture of PDMS and pHEMA in a 5:1 ratio; the lower contact lens encapsulation layer 2 is composed of 10:1 PDMS; the polyimide layer 3 is approximately 2.2 μm thick; and the intraocular pressure and temperature sensor layer 4 is 300~550 μm thick.

[0028] Figure 2The schematic diagram of the intraocular pressure and temperature sensor of the present invention is as follows: The outermost layer is the intraocular pressure sensor, which is composed of an intraocular pressure sensing element 5 and a gold electrode 6. The inner layer is the temperature sensor, which is in the shape of a double snake and is composed of a gold electrode 7. The lower layer of the whole device is based on a polyimide film 8. The circular enlargement 9 at the end of the intraocular pressure sensor is the connection point between the silver paste and the silver wire. The enlargement 10 at the end of the temperature sensor is the connection point between the silver paste and the silver wire.

[0029] Figure 4 The following is a schematic diagram of the connection between the present invention and silver paste and silver wire during application: A drop of silver paste 11 is applied to the enlarged end 9 of the intraocular pressure sensor using a cotton swab, and the silver wire 12 is quickly brought into contact with the silver paste 11. The connection method of the temperature sensor is the same as that of the intraocular pressure sensor.

[0030] Figure 5 The experimental verification results of the intraocular pressure sensor in this invention when applied to pig eyes are shown in the following figures: A. Under normal intraocular pressure fluctuation range, by changing the rate of intraocular pressure fluctuation, the resistance change rate characterized by the device shows good consistency with the actual intraocular pressure value; B. By gradually changing the intraocular pressure value, the resistance change rate remained consistent; C. Under normal intraocular pressure fluctuation range, simulating intraocular pressure fluctuation values ​​of 2 mmHg, 4 mmHg, 6 mmHg, 8 mmHg, and 10 mmHg respectively, the resistance change rate characterized by the device showed good consistency with the intraocular pressure fluctuation value; D. Based on Figure C, the resistance change rate curve with intraocular pressure fluctuation was prepared, and the linearity reached 0.9896, and the sensitivity reached 0.03% mmHg. -1 E. Under high intraocular pressure fluctuation range, the rate of change of resistance and the intraocular pressure value still have good consistency; F. Simulated long-term intraocular pressure fluctuation curves show good overlap between the rate of change of resistance and the intraocular pressure value curves.

[0031] Figure 6 The experimental verification results of the temperature sensor in this invention are shown in the figure: within the range of 30-50℃, the resistance change of the temperature sensor is 1.1Ω / ℃, and the temperature sensitivity coefficient is 0.3512.

[0032] Figure 7 The experimental results of the intraocular pressure sensor of the present invention being affected by temperature are shown in the figure: within 30-40℃, and more precisely within the range of ocular surface temperature variation (34.11~36.47℃), the resistance change of the intraocular pressure sensor is approximately 0.162%. This result indicates that the intraocular pressure sensor is affected in capturing small intraocular pressure fluctuations, but has little effect on changes above 5 mmHg. This result shows that it still has practical clinical application value.

Claims

1. A smart contact lens for collecting intraocular pressure and ocular surface temperature, characterized in that, This includes an intraocular pressure sensor and a temperature sensor; both are ring-shaped and located on the same type of eyeball surface; among which: The intraocular pressure sensor, located on the outer layer, consists of a sensing element and a gold electrode; the sensing element is a single-crystal silicon thin film. The temperature sensor is located in the inner layer and consists of two rings of double-stranded serpentine gold electrodes. A polyimide film is used as the lower coating layer, which has numerous radial serpentine connectors to connect the temperature sensor and the intraocular pressure sensor, maintaining the overall stability of the device. The enlarged circular ends of the intraocular pressure sensor and temperature sensor are the areas where silver paste and silver wire are fixed. The sensor layer and the lower encapsulation layer are encapsulated in two upper and lower spherical encapsulation layers to form a contact lens.

2. The smart contact lens according to claim 1, characterized in that: In the circular intraocular pressure sensor, the radius of the circular ring is 4~6mm, the thickness of the single crystal silicon thin film is 500~550nm, the linewidth is 75~150um, and its curvature is customizable; The gold electrode thickness is 150~200nm; the linewidth is greater than or equal to the silicon thin film linewidth, and the curvature is >3mm. -1 ; In the annular temperature sensor, the radius of the annulus is slightly smaller than that of the intraocular pressure sensor, ranging from 2 to 4 mm; the thickness of the gold electrode is 150 to 200 nm; the linewidth is 75 to 150 μm; and its curvature is >3 mm. -1 ; The lower polyimide film is coated with a thickness of 1.5~2.5um; the linewidth is slightly wider than that of the gold electrode and silicon film, at 100~200um.

3. The smart contact mirror according to claim 2, characterized in that, The upper encapsulation layer is a PDMS and pHEMA hybrid layer with a thickness of 50~250um, and the lower encapsulation layer is a PDMS layer with a thickness of 50~250um.

4. The method for preparing the smart contact lens according to any one of claims 1-3, characterized in that, The specific steps are as follows: (1) Spin coating and photolithography: Prepare a glass slide, spin-coat PMMA to prepare an adhesion layer with a thickness of 1.2 μm, and heat it; dilute polyimide (PI) to 2.5:1 and spin-coat to prepare a PI film with a thickness of 2.2 μm; (2) Transfer of silicon film: Prepare P-type silicon wafers, perform hydrofluoric acid pretreatment, and use the stamping method to transfer the single crystal silicon film onto the PI film; (3) Define the intraocular pressure sensing element: Define the silicon thin film according to the design pattern using ultraviolet lithography and reactive ion etching technology; (4) Define the electrodes of the intraocular pressure sensing element and the temperature sensor: Sputter chromium and gold targets using magnetron sputtering, and define the electrode pattern using ultraviolet lithography and wet etching techniques; (5) Overlaying the polyimide layer: Using ultraviolet lithography and reactive ion etching, the device overlay is completed according to the designed pattern; (6) Smart contact lens assembly: The finished device is immersed in acetone solution for 10 hours, and then transferred to the PDMS contact lens formed by the mold using water-soluble adhesive tape. Silver glue and silver wire are used for wire connection, and the upper device is encapsulated using a PDMS and pHEMA mixed solution at a ratio of 5:1.

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