Hemispherical intraocular pressure monitoring equipment and preparation method thereof

Abstract

The invention belongs to the technical field of flexible sensors, and particularly relates to hemispherical intraocular pressure monitoring equipment and a preparation method thereof. A Wheatstone bridge sensor is ingeniously designed according to an eyeball structure, and the design of a linear electrode and a snakelike electrode effectively captures the deformation of a cornea in the intraocular pressure change process, so that the sensitivity and precision of the intraocular pressure sensor are improved on the premise of not shielding a visual field; the P (VDF-TrFE) plastic substrate ensures the stability of the sensor, prevents the sensitive layer from generating microcracks when the cornea deformation is relatively large, and realizes a wide monitoring range of 0-50mmHg; the maskless laser etching technology avoids the situation that due to the fact that the defect of a mask plate exerts pressure stress on an electrode, microcracks inside a material expand, and then conductivity is reduced. The skeletonized electrode structure overcomes the mechanical limitation in the curved surface process of the two-dimensional substrate; the water transfer printing technology avoids electrode deformation or disconnection caused by deformation of a two-dimensional substrate in a traditional hot pressing method.

Description

Technical Field

[0001] The invention belongs to the technical field of flexible sensors, and in particular relates to a hemispherical intraocular pressure monitoring device and a preparation method thereof. Background Art

[0002] Glaucoma is the second leading cause of irreversible blindness, with nearly 80 million people affected worldwide in 2023, and this number is expected to increase to 118 million by 2041. 72% of glaucoma patients are diagnosed in the late stage, missing the best time for treatment. Therefore, it is very important to detect glaucoma early and take preventive measures. Therefore, increased intraocular pressure is considered to be the most obvious precursor symptom, and continuous monitoring of intraocular pressure can reduce the incidence of blindness caused by glaucoma. In addition, for postoperative patients undergoing myopia correction surgery (myopia correction surgery is increasing year by year and is expected to reach 5 billion cases by 2050) and the eye overuse group, the importance of immediate intraocular pressure monitoring is no less than that of glaucoma.

[0003] Intraocular pressure is a value that changes in real time and is affected by many factors, such as day and night changes, individual body position, mental stress, flu, etc. However, the commonly used intraocular pressure meters on the market generally have problems such as insufficient sensitivity, inability to measure in real time, expensive equipment and complex operation. Therefore, the development of a high-precision hemispherical intraocular pressure monitoring device has very important diagnostic and therapeutic significance and a very large market demand.

[0004] In order to achieve continuous intraocular pressure monitoring, researchers have tried to build various hemispherical intraocular pressure monitoring devices, such as using Wheatstone bridge structure varistors, using piezoresistive materials, or using strain local concentration strategies, etc. However, relatively speaking, the above strategies generally have disadvantages such as insufficient sensitivity and complex manufacturing procedures. Summary of the invention

[0005] In view of this, an object of the present invention is to provide a hemispherical intraocular pressure monitoring device and a preparation method thereof.

[0006] The technical solution of the present invention is:

[0007] A hemispherical intraocular pressure monitoring device, comprising an intraocular pressure sensor and a PDMS packaging layer, forming a cornea-like device (with a curvature radius of 8.4 or 8.6 mm);

[0008] The PDMS packaging layer includes an upper packaging layer 21 and a lower packaging layer 22, and the intraocular pressure sensor is located between the upper packaging layer 21 and the lower packaging layer 22;

[0009] The intraocular pressure sensor consists of a MXene sensitive layer (11) and a P (VDF-TrFE) substrate (12);

[0010] The intraocular pressure sensor is a Wheatstone bridge structure, consisting of two strain resistors (3) and two compensation resistors (4);

[0011] The intraocular pressure sensor is located in a circular area with a diameter of 9-13mm (corneoscleral junction) with the center of the pupil as the center, to monitor the changes in intraocular pressure to the greatest extent without blocking the field of vision;

[0012] In the Wheatstone bridge structure, the two strain resistors (3) are designed in the direction of the ring and are in a straight line shape so as to follow the change of intraocular pressure to the greatest extent; the two compensation resistors (4) are designed in the radial direction perpendicular to the direction of the ring and are in a serpentine shape so as not to change with the change of intraocular pressure; the initial length and width of the arms of the two strain resistors (3) and the two compensation resistors (4) are the same;

[0013] Among them, for intraocular pressure monitoring, the sensitivity of this device is not less than 12mV mmHg -1 , linearity is not less than 0.9896; effective resolution is 0.05mmHg, and measurement error is not more than 1.5%.

[0014] A method for preparing a hemispherical intraocular pressure monitoring device, comprising:

[0015] S1: coating and drying a P(VDF-TrFE) solution on a clean glass sheet to form a P(VDF-TrFE) substrate film, and then spraying a MXene solution on the P(VDF-TrFE) substrate film to obtain a MXene sensitive layer film located above the P(VDF-TrFE) substrate film;

[0016] S2: Use laser to etch the electrode outline on the P(VDF-TrFE) substrate film and the MXene sensitive layer film, peel off the part outside the electrode outline, and form the P(VDF-TrFE) substrate and the MXene sensitive layer electrode above;

[0017] S3: Spin-coat a water-soluble film on a glass sheet containing the P(VDF-TrFE) substrate and the MXene sensitive layer electrode above and dry it;

[0018] S4: remove the water-soluble film, P(VDF-TrFE) substrate and the MXene sensitive layer electrode above from the glass slide;

[0019] S5: drop-coating a PDMS solution on the hemispherical metal mold and drying the solution to form a PDMS film, i.e., the lower encapsulation layer 22;

[0020] S6: The water-soluble film with the P(VDF-TrFE) substrate and the MXene sensitive layer electrode removed in step S4 is vertically washed with water above the hemispherical metal mold containing the PDMS film, and the P(VDF-TrFE) substrate and the MXene sensitive layer electrode are transferred to the hemispherical PDMS encapsulation layer;

[0021] S7: drip PDMS solution on the PDMS encapsulation layer containing the P(VDF-TrFE) substrate and the MXene sensitive layer electrode and dry it to form an upper encapsulation layer 21, thereby completing the preparation of the hemispherical intraocular pressure monitoring device.

[0022] The thickness of the hemispherical intraocular pressure monitoring device is 100 to 300 μm.

[0023] The thickness of the MXene sensitive layer is 10 to 100 nm.

[0024] The thickness of the P(VDF-TrFE) substrate is 10 to 60 μm.

[0025] The thickness of the PDMS encapsulation layer is 40 to 10 to 130 μm.

[0026] The two strain resistors are designed in the direction of the ring and are in a straight line shape; the two compensation resistors are designed in a radial direction perpendicular to the direction of the ring and are in a serpentine shape; the width of each resistor is 10 μm to 500 μm.

[0027] The angle of each serpentine shape of the compensation resistor is 30° to 180°.

[0028] In step S1, the rotation speed of spin coating P(VDF-TrFE) solution is 1000-3000 rpm, and the time is 5-10 s;

[0029] In step S1, the P(VDF-TrFE) solution is dried at a temperature of 30-60°C for a time of 10-30 minutes;

[0030] In step S1, the MXene solution is applied by dripping or spraying;

[0031] The temperature for drying the MXene solution in step S1 is 30-60°C;

[0032] In step S2, the speed of laser etching the electrode contour is 1000 to 3000 mm / s, the current is 1 to 5 amps, and the number of times is 1 to 10 times.

[0033] In step S3, the water-soluble film is polyethylene oxide (PEO), polyvinyl alcohol (PVA), etc.;

[0034] In step S3, the rotation speed of spin coating the water-soluble film is 100-1000 rpm, and the time is 5-10 s;

[0035] In step S3, the water-soluble film is dried at a temperature of 30-60° C. for a time of 10-30 minutes.

[0036] In step S5, the ratio of the main agent to the curing agent in the PDMS solution is 5:1 to 20:1;

[0037] In step S5, the PDMS solution is dried at a temperature of 90-150° C. for a time of 10-30 min.

[0038] Beneficial Effects

[0039] 1. The Wheatstone bridge sensor is cleverly designed according to the structure of the eyeball. The design of the linear electrode and the serpentine electrode effectively captures the deformation of the cornea during the change of intraocular pressure. Therefore, the hemispherical intraocular pressure monitoring device in the embodiment of the present invention further improves the sensitivity and accuracy of the intraocular pressure sensor without blocking the visual field.

[0040] 2. The P (VDF-TrFE) plastic substrate ensures the stability of the sensor, avoids microcracks in the sensitive layer when the cornea is deformed greatly, and achieves a wide monitoring range of 0-50 mmHg;

[0041] 3. The preparation method of the hemispherical intraocular pressure monitoring device is advanced. The maskless laser etching technology avoids the defects of the mask plate that apply compressive stress to the electrode, causing the expansion of microcracks inside the material and thus leading to a decrease in conductivity; the skeletonized electrode structure overcomes the mechanical limitations in the process of curvature of the two-dimensional substrate; the water transfer technology avoids the deformation or disconnection of the electrode caused by the deformation of the two-dimensional substrate in the traditional hot pressing method. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 is a schematic diagram of the structure layering of a high-precision hemispherical intraocular pressure monitoring device in an embodiment of the present invention;

[0043] Figure 2 is a schematic diagram of the Wheatstone bridge structure in an embodiment of the present invention;

[0044] Figure 3 is the relationship between the current change and the tensile strain of the straight electrode and the serpentine electrode in the embodiment of the present invention;

[0045] Figure 4 It is a microscopic schematic diagram of the MXene nanosheet in the initial state and under tensile stress and a schematic diagram of the change of the electron transfer channel in an embodiment of the present invention;

[0046] Figure 5 It is the relationship between the sensor sensitivity and the thickness of the MXene sensitive layer under 1% strain recovery in the embodiment of the present invention;

[0047] Figure 6 is the statistical distribution of the output voltage of the hemispherical intraocular pressure monitoring device in the embodiment of the present invention at 0.05, 0.1, 0.15, 0.2 and 0.25 mmHg;

[0048] Figure 7 It is a statistical analysis of the accuracy of the hemispherical intraocular pressure monitoring device under a pressure of 0.2 mmHg in an embodiment of the present invention;

[0049] Figure 8 It is the relationship between the change in output voltage (ΔV) and pressure of the hemispherical intraocular pressure monitoring device in the embodiment of the present invention. DETAILED DESCRIPTION

[0050] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in combination with specific embodiments and with reference to the accompanying drawings, but this should not be construed as limiting the scope of protection of the present invention.

[0051] Embodiment 1:

[0052] A method for preparing a linear electrode and a serpentine electrode, comprising:

[0053] S1: Spin coating the P(VDF-TrFE) solution on a clean glass slide at a rotation speed of 2500 rpm for 10 seconds and drying at a temperature of 50°C for 30 minutes to obtain a P(VDF-TrFE) substrate film (12);

[0054] S2: Spin coating the PDMS solution on the P(VDF-TrFE) substrate film (12) at a rotation speed of 1500 rpm for 10 seconds and drying at a temperature of 100° C. for 30 minutes to obtain a lower encapsulation layer (22);

[0055] In step S2, the ratio of the main agent to the curing agent in the PDMS solution is 8:1;

[0056] S3: peeling off the P(VDF-TrFE) substrate film (12) and the lower encapsulation layer (22) from the glass sheet and attaching the reverse side thereof to the glass sheet, the order from bottom to top being the glass sheet, the lower encapsulation layer (22) and the P(VDF-TrFE) substrate film (12);

[0057] S4: using ultraviolet laser to etch straight electrode and serpentine electrode contours on the P(VDF-TrFE) substrate film (12) three times at a speed of 1000 mm / s and a current of 2A;

[0058] S5: Spray 1 mL of 3 mg / mL MXene solution on the P(VDF-TrFE) substrate film (12) containing the electrode contour to obtain a MXene linear electrode and a serpentine electrode located above the P(VDF-TrFE) substrate film (12). The heating temperature during the spraying process is 60° C. After the spraying is completed, the P(VDF-TrFE) substrate film and MXene outside the electrode contour are peeled off to form a linear electrode and a serpentine electrode.

[0059] In step S5, the width of the linear electrode and the serpentine electrode is 100 μm, and the angle of the serpentine electrode is 180°;

[0060] S6: Spin-coating the PDMS solution on the lower packaging layer (22) containing the linear electrode and the serpentine electrode at a rotation speed of 1500 rpm for 10 seconds and drying at a temperature of 100° C. for 30 minutes to obtain an upper packaging layer (21);

[0061] S7: Cut the packaged electrodes into electrodes with a width of 0.5 cm and a length of 2 cm, completing the preparation of linear electrodes and serpentine electrodes.

[0062] The linear electrodes and serpentine electrodes prepared in steps S1-S7 were subjected to a tensile test, and the steps were as follows: the electrode was vertically clamped on the tensile table and kept in a relaxed state, then a voltage of 1 V was connected to the electrode, and finally the electrode was pulled up at a uniform speed, and the current change of the electrode was recorded. Figure 3 The current-strain curve in the figure shows that under the same strain, the current change of the linear electrode is much larger than that of the serpentine electrode. When stretched to 9%, the linear electrode is already in a short circuit state. Therefore, the strain resistor is linear and designed in the circumferential direction, which can follow the changes in intraocular pressure to a greater extent. The compensation resistor is serpentine and designed in the radial direction, and hardly changes with the changes in intraocular pressure, thereby enabling the sensor to obtain higher accuracy and sensitivity.

[0063] The main reason for the change in electrode current during the process of applying stress to the electrode is that the slip phenomenon of MXene nanosheets in the sensitive layer based on weak van der Waals force under stress reduces the electron transfer channel and increases the electrode resistance. At the same time, under the action of applied load, the friction that determines the degree of slip induces a high dipole potential on the interlayer potential energy surface, thereby inhibiting the interlayer electron transfer behavior, thereby increasing the resistance change of the sensitive layer under stress and improving the sensitivity, such as Figure 4 As shown in the schematic diagram.

[0064] For steps S1-S7, a series of linear electrodes were prepared by changing the thickness of the MXene sensitive layer, with resistances of 9 kΩ, 12 kΩ, 27 kΩ, 193 kΩ, 250 kΩ, 304 kΩ and 353 kΩ, respectively. Stress was applied to each electrode to cause a 1% deformation and then restore it to the nurse length, and the resistance change of each electrode was recorded. Figure 5 The curve of resistance change with initial resistance shows that when the MXene sensitive layer is stretched by 1%, the mechanical sensitivity first increases and then decreases with the increase of thickness. Therefore, when the initial resistance of the electrode is controlled at about 250kΩ, the intraocular pressure monitoring device has the highest sensitivity.

[0065] Example 2

[0066] A hemispherical intraocular pressure monitoring device ( Figure 1 ), mainly comprising an intraocular pressure sensor (1) and a PDMS packaging layer (2), forming a cornea-like device with a curvature radius of 8.4 as a whole, and the total thickness of the device is 180 μm; wherein: the intraocular pressure sensor is composed of a MXene sensitive layer (11) and a P (VDF-TrFE) substrate (12); the thickness of the MXene sensitive layer (11) is 60 nm, and the initial resistance is 250 kΩ; the thickness of the P (VDF-TrFE) substrate is 20 μm.

[0067] The intraocular pressure sensor is a Wheatstone bridge structure ( Figure 2 ), composed of 2 strain resistors (3) and 2 compensation resistors (4), the designed bridge structure is limited to a circular area with a diameter of 9-13mm (corneoscleral junction) with the center of the pupil as the center, so as to monitor the changes in intraocular pressure to the greatest extent without blocking the visual field; wherein: the two strain resistors (3) are designed in the direction of the circular ring and are in a straight line shape to follow the changes in intraocular pressure to the greatest extent; the two compensation resistors (4) are designed in a radial direction perpendicular to the direction of the circular ring and are in a serpentine shape with an angle of 180°, which hardly change with the changes in intraocular pressure; the initial lengths of the four resistors in the bridge are all 37.4mm and the widths are all 100μm.

[0068] A method for preparing a hemispherical intraocular pressure monitoring device, comprising:

[0069] S1: Spin-coat a P(VDF-TrFE) solution on a clean glass slide at a rotation speed of 2500 rpm for 10 seconds and dry at a temperature of 50°C for 30 minutes to obtain a P(VDF-TrFE) substrate film (12), and then spray-coat 1 mL of a 3 mg / mL MXene solution on the P(VDF-TrFE) substrate film (12) to obtain a MXene sensitive layer film (11) located above the P(VDF-TrFE) substrate film (12). The heating temperature during the spraying process is 60°C;

[0070] S2: using ultraviolet laser to etch the electrode outline on the P(VDF-TrFE) substrate film (12) and the MXene sensitive layer film (11) three times at a speed of 1000 mm / s and a current of 2A, and peeling off the part outside the electrode outline to form a sensor (1);

[0071] S3: Spin-coat the glass slide containing the sensor (1) with a polyethylene oxide (PEO) solution at 500 rpm for 10 s and dry at 40°C for 30 min;

[0072] S4: Transfer the water-soluble film and the sensor (1) together.

[0073] S5: drop-coating a PDMS solution on the hemispherical metal mold and drying it at 120° C. for 25 min to obtain a lower encapsulation layer (22);

[0074] In step S5, the ratio of the main agent to the curing agent in the PDMS solution is 8:1

[0075] S6: The transferred water-soluble film and sensor (1) are vertically rinsed with water above the hemispherical metal mold containing the lower packaging layer (22), and the sensor (1) is transferred to the hemispherical PDMS lower packaging layer (22);

[0076] S7: A second layer of PDMS solution (21) is drop-coated on the lower packaging layer (22) containing the sensor (1) and dried at 120°C for 25 minutes to form an upper packaging layer (22), thereby completing the production of the hemispherical intraocular pressure monitoring device.

[0077] According to steps S1-S7, 10 hemispherical intraocular pressure monitoring devices were prepared and tested for 80 cycles at pressures of 0-0.05 mmHg, 0-0.1 mmHg, 0-0.15 mmHg, 0-0.2 mmHg, and 0-0.25 mmHg, respectively. Figure 6 The output voltage change and the corresponding statistical graph show that each pressure corresponds to a relatively fixed output voltage change and there is a large gap between the output voltage changes corresponding to each pressure, indicating that the effective resolution of the device can reach 0.05mmHg.

[0078] According to steps S1-S7, 15 hemispherical intraocular pressure monitoring devices were prepared, and each device was tested for 80 cycles at a pressure of 0-0.2 mmHg. Figure 7 The accuracy statistical analysis shown indicates that the accuracy of the hemispherical IOP monitoring device is 1.075%.

[0079] Furthermore, cyclic tests were performed at pressures of 0-10 mmHg, 0-20 mmHg, 0-30 mmHg, 0-40 mmHg and 0-50 mmHg, and a linear fit was performed on the output voltage changes obtained in each test. Figure 8 The fitting curve shows that the monitoring range of the hemispherical intraocular pressure monitoring device in the present invention is 0-50 mmHg, the output voltage (ΔV) change has a good linear relationship with the pressure, and the linear regression coefficient R 2 =0.998, and 12.52 mV mmHg during pressure increase -1 High sensitivity.

[0080] In summary, the above are only preferred embodiments of the present invention and are not intended to limit the protection scope of 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. A hemispherical intraocular pressure monitoring device, characterized in that: The hemispherical intraocular pressure monitoring device includes an intraocular pressure sensor and a PDMS packaging layer; The PDMS packaging layer includes an upper packaging layer and a lower packaging layer, and the intraocular pressure sensor is located between the upper packaging layer and the lower packaging layer; The intraocular pressure sensor is composed of two strain resistors and two compensation resistors to form a Wheatstone bridge structure; The two strain resistors in the Wheatstone bridge structure are designed on a circular ring and are in a linear shape to monitor intraocular pressure changes to the greatest extent; The two compensation resistors in the Wheatstone bridge structure are designed in a radial direction perpendicular to the ring and have a serpentine shape, which does not change with changes in intraocular pressure; The circular ring is an area with a diameter of 9-13 mm and a pupil center as the center.

2. A hemispherical intraocular pressure monitoring device according to claim 1, characterized in that: The initial lengths and widths of the arms of the two strain resistors and the two compensation resistors are the same.

3. A hemispherical intraocular pressure monitoring device according to claim 1, characterized in that: The sensitivity of monitoring intraocular pressure changes is not less than 12mV mmHg -1 , the linearity is not less than 0.9896, the effective resolution is 0.05mmHg, and the measurement error is not more than 1.5%.

4. The hemispherical intraocular pressure monitoring device according to claim 1, characterized in that: The hemispherical intraocular pressure monitoring device is a cornea-like device with a curvature radius of 8.4 or 8.6 mm.

5. The hemispherical intraocular pressure monitoring device according to claim 1, characterized in that: The intraocular pressure sensor consists of a MXene sensitive layer and a P(VDF-TrFE) substrate.

6. A method for preparing a hemispherical intraocular pressure monitoring device, characterized in that The steps of the method include: S1, coating a P(VDF-TrFE) solution on a glass sheet, forming a P(VDF-TrFE) substrate film after drying, and then spraying a MXene solution on the P(VDF-TrFE) substrate film to obtain a MXene sensitive layer film located above the P(VDF-TrFE) substrate film; S2, using a laser to etch the electrode outline on the P(VDF-TrFE) substrate film and the MXene sensitive layer film, peeling off the part outside the electrode outline to form the P(VDF-TrFE) substrate and the MXene sensitive layer electrode above; S3, spin coating a water-soluble film on a glass sheet containing a P(VDF-TrFE) substrate and an upper MXene sensitive layer electrode and drying; S4, removing the water-soluble film, the P(VDF-TrFE) substrate and the MXene sensitive layer electrode above from the glass sheet; S5, drop-coating a PDMS solution on the hemispherical metal mold, and drying to form a PDMS film to obtain a lower encapsulation layer 22; S6, vertically flushing the water-soluble film with the P(VDF-TrFE) substrate and the MXene sensitive layer electrode removed in step S4 above the lower packaging layer obtained in step S5 with water flow, and the P(VDF-TrFE) substrate and the MXene sensitive layer electrode are transferred to the hemispherical PDMS packaging layer; S7, drop-coating a PDMS solution on the PDMS encapsulation layer containing the P(VDF-TrFE) substrate and the MXene sensitive layer electrode and drying the solution to form an upper encapsulation layer, thereby completing the preparation of the hemispherical intraocular pressure monitoring device.

7. The method for preparing a hemispherical intraocular pressure monitoring device according to claim 6, characterized in that: The thickness of the hemispherical intraocular pressure monitoring device is 100 to 300 μm; The thickness of the MXene sensitive layer is 10 to 100 nm; The thickness of the P(VDF-TrFE) substrate is 10 to 60 μm; The thickness of the PDMS encapsulation layer is 40 to 10 to 130 μm.

8. The method for preparing a hemispherical intraocular pressure monitoring device according to claim 6, characterized in that: The two strain resistors are designed in the direction of the ring and are in a straight line shape; the two compensation resistors are designed in a radial direction perpendicular to the direction of the ring and are in a serpentine shape; The width of each resistor is 10 μm to 500 μm; The angle of each serpentine shape of the compensation resistor is 30° to 180°.

9. The method for preparing a hemispherical intraocular pressure monitoring device according to claim 6, characterized in that: In the step S1, the rotation speed of spin coating the P(VDF-TrFE) solution is 1000-3000 rpm, and the time is 5-10 s; In the step S1, the P(VDF-TrFE) solution is dried at a temperature of 30-60°C for a time of 10-30 minutes; In the step S1, the MXene solution is applied by dripping or spraying; In step S1, the MXene solution is dried at a temperature of 30-60°C; In the step S2, the speed of laser etching the electrode contour is 1000 to 3000 mm / s, the current is 1 to 5 amps, and the number of times is 1 to 10.

10. The method for preparing a hemispherical intraocular pressure monitoring device according to claim 6, characterized in that: In step S3, the water-soluble film is polyethylene oxide or polyvinyl alcohol; In step S3, the rotation speed of spin coating the water-soluble film is 100-1000 rpm, and the time is 5-10 s; In step S3, the water-soluble film is dried at a temperature of 30-60° C. for 10-30 minutes; In the step S5, the ratio of the main agent to the curing agent in the PDMS solution is 5:1 to 20:1; In the step S5, the PDMS solution is dried at a temperature of 90-150° C. for a time of 10-30 min.

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