CN105962887B - A kind of non-intrusion type detection of eyeball tension sensor based on micro-fluidic technologies - Google Patents

Abstract

The invention discloses a non-invasive intraocular pressure detection sensor based on microfluidic technology, which comprises a corneal contact lens, a spiral inductance, an edge capacitor and an inner ring capacitor, wherein a cavity and a microfluidic channel are arranged inside the contact lens; the cavity The body is connected with the microfluidic channel for storing fluid and delivering fluid to the microfluidic channel; the amount of fluid transported in the microfluidic channel is affected by intraocular pressure, and the capacitance value of the inner ring capacitor varies with the microfluidic channel. The amount of fluid delivered varies; through the CLC circuit composed of fringe capacitance, spiral inductance and inner ring capacitance, the detection of intraocular pressure is realized. The intraocular pressure detection sensor in the present invention can effectively solve the problem that the intraocular pressure sensor is not convenient for night monitoring, realize high-precision, 24-hour full-range measurement of intraocular pressure fluctuations, and has the advantages of simple structure, convenient manufacture, high sensitivity, and large dynamic range. advantage.

Description

A non-invasive intraocular pressure detection sensor based on microfluidic technology

technical field

The invention belongs to the technical field of medical devices, and more specifically relates to a non-invasive intraocular pressure detection sensor based on microfluidic technology. The intraocular pressure detection sensor adopts a C-L-C structure and is a wireless passive non-invasive Eye pressure detection sensor.

Background technique

Glaucoma is the world's first irreversible blinding eye disease. Medical research shows that glaucoma is a disease characterized by optic nerve damage and visual field defects due to pathological elevated intraocular pressure. The increase in intraocular pressure is an important indicator for the diagnosis and treatment of glaucoma, and studies have shown that the intraocular pressure of glaucoma patients fluctuates greatly within 24 hours, and generally reaches the peak during sleep and early morning. No intraocular pressure measurement will be performed. Therefore, it is of great significance to realize the 24-hour detection of intraocular pressure. Currently, sensors capable of measuring intraocular pressure 24 hours a day are being studied by countries all over the world, including invasive intraocular pressure sensors and non-invasive intraocular pressure sensors.

Invasive intraocular pressure sensors mostly use the wireless passive sensor form of the "L-C resonant circuit" principle. The sensor is miniaturized through MEMS processing technology and invaded into the eye through surgery. It has the characteristics of complex system, high heat generation, and discomfort. At the same time, its use invades the interior of the eye, which may cause irreversible damage to the eye. Non-invasive intraocular pressure sensors generally integrate the sensor into the contact lens, and use a wireless passive method to measure corneal deformation, thereby corresponding to the corresponding intraocular pressure. The 24-hour intraocular pressure measurement in the prior art uses "L-C resonant circuit" and also uses strain gauges, both of which are currently in the laboratory stage. Recently, the United States proposed a non-invasive intraocular pressure sensor using microfluidic technology. The position of the microfluid in the microchannel is determined by image processing by taking pictures, which has the disadvantages of expensive equipment, complex algorithm processing, and the inability to measure the intraocular pressure at night when people are sleeping and the intraocular pressure reaches its peak. . However, the Chinese patent document "Wireless Passive Non-Invasive MEMS Intraocular Pressure Sensor and Its Manufacturing Method (Patent Application No.: 201510065578.X)" adopts a C-L-C structure sensor, which is easy to manufacture, but it realizes intraocular pressure by changing the capacitance distance. measurement with low sensitivity.

Contents of the invention

In view of the above defects or improvement needs of the prior art, the purpose of the present invention is to provide a non-invasive intraocular pressure detection sensor based on microfluidic technology, in which the structure, material and connection between the various components critical to it Compared with the existing technology, it can effectively solve the problem that the intraocular pressure sensor is not convenient for night monitoring, and realize high-precision, 24-hour full-range measurement of intraocular pressure fluctuations.

In order to achieve the above object, the present invention provides a non-invasive intraocular pressure detection sensor based on microfluidic technology, which is characterized in that it includes a contact lens, a spiral inductor, an edge capacitor and an inner ring capacitor, wherein,

The contact lens is spherically crowned and adapted to conform to the shape of the patient's eyeball when worn;

Both the fringe capacitance and the spiral inductance are located on the contact lens; the spiral inductance is distributed in a spiral shape, and the projection of the fringe capacitance on the plane where the circular edge of the contact lens is located is located on the spiral inductance. the outer portion of the helical projection on the plane in which the rounded edge of the contact lens lies;

The inner ring capacitor is located on the contact lens, and the projection of the inner ring capacitor on the plane where the circular edge of the contact lens is located is located on the plane where the spiral inductor is located on the circular edge of the contact lens The interior of the spiral projection of ;

One end of the spiral inductor is connected to one end of the fringe capacitor, the other end of the spiral inductor is connected to one end of the inner ring capacitor; the other end of the fringe capacitor is connected to the other end of the inner ring capacitor;

A cavity and a microfluidic channel are arranged inside the contact lens; the cavity communicates with the microfluidic channel for storing fluid and transporting the fluid into the microfluidic channel; The amount of the fluid delivered is affected by intraocular pressure, and the capacitance value of the inner ring capacitor changes with the amount of the fluid delivered in the microfluidic channel; through the fringe capacitance, the spiral inductance and the The CLC loop formed by the inner ring capacitor realizes the detection of the intraocular pressure.

As a further preference of the present invention, the non-invasive intraocular pressure detection sensor based on microfluidic technology further includes a receiving coil, which is used to detect The resonant frequency of the CLC circuit, and judge the magnitude of intraocular pressure according to the detected resonant frequency.

As a further preference of the present invention, the inner ring capacitor is a flat capacitor, and the microfluidic channel is located between two capacitor plates of the flat capacitor.

As a further preference of the present invention, the capacitance value of the fringe capacitor is at least 4 times the capacitance value of the inner ring capacitor; preferably, the inductance value of the spiral inductor is 50nH to 500nH, and the capacitance value of the fringe capacitor is 46.9pF-71.4pF, and the capacitance value of the inner ring capacitor is 10.7pF-16.05pF.

As a further preference of the present invention, there are multiple cavities, all of which are located inside the contact lens, and the centers of the cavities are on the plane where the circular edge of the contact lens is located. The projections are distributed along the circumference of a circle concentric with the circular edge of the contact lens.

As a further preference of the present invention, the size specification of the contact lens is set to a diameter of 13mm-18mm.

As a further preference of the present invention, the microfluidic channel has a height of 10 μm-30 μm, a width of 20 μm-80 μm, and a total length of 40 mm-100 mm.

As a further preference of the present invention, the fluid is glycerin, water or room temperature ionic liquid.

As a further preference of the present invention, the contact lens is composed of a hard layer and a soft layer; the soft layer is used for direct contact with the patient's eyeball when the contact lens is worn, preferably, the soft layer The hard layer is made of PDMS material; the thickness of the hard layer is 60 μm to 80 μm, and the overall thickness of the contact lens is not more than 300 μm; the microfluidic channel, the spiral inductor, the fringe capacitance and the inner ring Capacitors are located in the hard layer. Preferably, the hard layer is made of parylene, PMMA, PC or PET.

As a further preference of the present invention, the cavity is in the shape of a cylinder, the height of the cylinder is 80 μm-150 μm, and the radius is 0.5 mm-1 mm.

Through the above technical scheme conceived by the present invention, compared with the prior art, since the C-L-C structure based on microfluidic technology is used to form a wireless passive non-invasive intraocular pressure detection sensor, it has the advantages of simple structure, convenient manufacture, high sensitivity, dynamic Large range, good stability, simple detection and so on. The present invention adjusts the intraocular pressure sensing method, based on the principle of microfluidic variable medium capacitance, not only maintains the characteristics of the original CLC structure, which is convenient for preparation, avoids the cross-layer wire bonding connection of capacitance and inductance, but also makes the sensor have Very high detection sensitivity.

In the present invention, fringe capacitance, spiral inductance and inner-ring capacitance are connected in series to form a CLC circuit. The fringe capacitance, spiral inductance and inner-ring capacitance all have two wire ends, and one end of the spiral inductance is connected to one end of the fringe capacitance. The other end of the spiral inductor is connected to one end of the inner ring capacitor, and the other end of the fringe capacitor is connected to the other end of the inner ring capacitor, thereby forming a CLC loop. The inner ring capacitor is preferably a flat plate capacitor, and a microfluidic channel is distributed between the two capacitor plates of the inner ring capacitor, and the liquid microfluid is distributed in the microfluidic channel and the microcavity; affected by the real-time intraocular pressure, in the microfluidic channel The amount of liquid microfluid in the channel will change, affecting the capacitance value of the inner ring capacitor, and finally affecting the resonant frequency of the CLC circuit. When the intraocular pressure of the patient changes, it will cause the deformation of the corneal contact lens, causing the extrusion and suction deformation of the microcavity, thereby realizing the movement of liquid microfluid in the microfluidic channel, and the microfluidic channel is distributed in the dielectric layer of the inner ring capacitor , due to the movement of the liquid microfluid, the dielectric constant between some inner ring capacitors changes, thereby realizing the change of the resonant frequency of the C-L-C loop. Externally, the resonant frequency detection is realized by using a network analyzer, such as antenna inductance frequency sweep, so as to realize intraocular pressure detection. Specifically, when the patient's intraocular pressure increases, the microfluid in the microcavity is squeezed into the microchannel; when the patient's intraocular pressure decreases, a partial vacuum is formed in the microcavity, and since the end of the microchannel is connected to the atmosphere, the atmospheric pressure The microfluid is directly pressed back into the microcavity; since the total volume of the liquid in the microcavity and the microchannel remains unchanged, a dynamic balance is formed, and the microcavity is equivalent to a pump.

In the present invention, the height of the microfluidic channel is 10 μm to 30 μm, the width is 20 μm to 80 μm, and the total length is 40 mm to 100 mm; the height of the cylindrical cavity is 80 μm to 150 μm, and the radius is 0.5 mm to 1 mm; the initially set edge The capacitance value of the capacitor is more than 4 times the capacitance value of the inner ring capacitor. For example, the inductance value of the spiral inductor is 50nH~500nH, the initial capacitance value of the edge capacitor is 46.9pF~71.4pF, and the initial capacitance value of the inner ring capacitor is 10.7pF ~ 16.05pF, through cooperation with microfluidic channels (including microcavities, etc.), it can measure intraocular pressure in the range of 0-65mmHg, and has high detection sensitivity. The projection of the spiral inductance on the plane where the circular edge of the contact lens is located is a helix, the projection of the fringe capacitance on the plane where the circular edge of the contact lens is located is located outside the helix, and the inner ring capacitance is in the circle of the contact lens. The projection on the plane of the edge of the shape is inside the helix shape.

The hard layer in the intraocular pressure sensor of the present invention (such as using Parylene-C material, etc.) is not easily deformed, so that the liquid can be squeezed more into the microchannel. The microfluidic channels, spiral inductors, edge capacitors, and inner ring capacitor structures are distributed in the hard layer. When no fluid enters the microchannels, the capacitance and inductance values are not easy to change, which improves the detection accuracy. In the present invention, glycerin, water or ionic liquid are preferably used as liquid microfluids. Glycerin is a liquid with a high dielectric constant and is harmless to human eyes. The sensor has good sensitivity.

In summary, the non-invasive intraocular pressure detection sensor based on microfluidic technology in the present invention adopts the C-L-C structure, which is a wireless, passive, non-invasive intraocular pressure detection sensor, which can realize all-weather measurement of intraocular pressure, and at the same time dielectrics such as glycerin The constant is high, the sensor has the characteristics of high sensitivity and wide dynamic range.

Description of drawings

Fig. 1 (a) is the top view structure schematic diagram of the non-invasive intraocular pressure detection sensor based on microfluidic technology of the present invention;

Fig. 1 (b) is the top view structure schematic diagram of the microcavity of the non-invasive intraocular pressure detection sensor based on microfluidic technology of the present invention;

Fig. 2 is a cross-sectional view of the intraocular pressure sensor, which is unfolded into a plane display;

Fig. 3 is a schematic diagram of the layered manufacturing principle of the intraocular pressure sensor, and each layer is unfolded into a plane display;

Fig. 4 is an overall schematic diagram of the non-invasive intraocular pressure detection sensor based on microfluidic technology of the present invention, including a spherical contact lens and other components of the intraocular pressure sensor integrated in the contact lens.

The meanings of each reference sign in the figure are as follows: 1 is a contact lens, 2 is a hard layer, 3 is a soft layer, 4 is a microfluidic channel (ie, a microfluidic channel, a microchannel), and 5 is a liquid microfluidic (ie, a microfluidic channel). Fluid), 6 is a microcavity (that is, a cavity), 7 is a spiral inductor, 8 is a fringe capacitance, and 9 is an inner ring capacitance.

detailed description

In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not constitute a conflict with each other.

Example 1

As shown in Figure 1(a) and Figure 2, the non-invasive intraocular pressure detection sensor based on microfluidic technology in the present invention is a C-L-C structure wireless passive non-invasive intraocular pressure sensor based on microfluidic technology Detection sensors, including soft contact lenses, hard layers, soft layers, microfluidic channels (ie, microchannels), liquid microfluidics, microcavities, spiral inductors, fringe capacitance, and inner ring capacitance, among which:

The contact lens has a spherical crown as a whole, and is used to fit the patient's eyeball shape when worn; the contact lens is composed of a hard layer and a soft layer, and the soft layer directly interacts with the patient's cornea. Fitting; the size of the contact lens is set to be 13mm-18mm in diameter; the thickness of the hard layer is 60-80μm, and the main body is made of parylene-c (ie C-type parylene) material, which is not easy to deform; the soft layer The PDMS material is used, which has high oxygen permeability, and its surface can be ionically modified to make it biocompatible, suitable for corneal wear; the overall thickness of the contact lens is less than 300 μm.

Microfluidic channels, spiral inductors, fringe capacitors, and inner ring capacitor structures are distributed in the hard layer; the microcavity can be composed of small cavities distributed in the hard layer and the soft layer (for example, it can be composed of the hard layer and the soft layer. Layers together form a microcavity, a part of the microcavity wall is composed of a hard layer, and a part is composed of a soft layer);

The microfluidic channel is distributed in the dielectric layer of the inner ring capacitor; the height of the microchannel can be 10 μm to 30 μm, the width can be 20 μm to 80 μm, and the overall length can be 40 mm to 100 mm.

The liquid microfluid is distributed in the microfluidic channel and the microcavity; the liquid microfluid can be a liquid with a high dielectric constant such as glycerin and is harmless to human eyes, which can be miscible with water to form a solution with a certain viscosity to flow in the microchannel.

The height of the microcavity is 80 μm to 150 μm, there may be multiple microcavities, and the multiple microcavities are connected. The microcavity is composed of a hard layer and a soft layer. Several are arranged in a ring and interconnected together, so that the maximum deformation of the contact lens with the increase of intraocular pressure can be felt, and there is liquid in the initial microcavity. The microfluidic fluid such as glycerin can be injected from here, and the microcavity is "sewn" after injection. The microfluidic channel connected to the microcavity has an open end and is exposed on the outer surface of the corneal lens, directly communicating with the atmosphere; when the intraocular pressure of the patient changes, the contact lens is deformed and the microcavity is squeezed and closed deformation, thereby realizing the movement of the liquid microfluid in the microfluidic channel, and the microfluidic channel is distributed in the dielectric layer of the inner ring capacitor. Due to the movement of the liquid microfluid, the dielectric constant between some inner ring capacitors changes, thereby Realize the change of the resonant frequency of the C-L-C circuit, and realize the intraocular pressure detection by detecting the resonant frequency externally. Specifically, when the patient's intraocular pressure increases, the microfluid in the microcavity is squeezed into the microchannel; when the patient's intraocular pressure decreases, a partial vacuum is formed in the microcavity, and since the end of the microchannel is connected to the atmosphere, the atmospheric pressure The microfluid is directly pressed back into the microcavity; since the total volume of the liquid in the microcavity and the microchannel remains unchanged, a dynamic equilibrium is formed, and the microcavity is equivalent to a pump.

As shown in Figure 1 (b), it is connected with the microchannel of the hard layer, that is, the interface directly connected with the microfluidic channel between the two electrode plates of the plate capacitor; the centers of multiple microcavities are in the circle of the contact lens. The projection on the plane where the edge of the shape is located is distributed along the circumference of a circle concentric with the circular edge of the contact lens (there can be multiple concentric circles, as shown in Figure 1 (b)), and is located between the two electrode plates of the flat capacitor The projection of the microfluidic channel on the plane can be either inside the concentric circle or outside the concentric circle, and only need to adjust the corresponding interface position connected with the hard layer microchannel.

The above-mentioned spiral inductance, fringe capacitance and inner ring capacitance are connected in series to form a C-L-C resonant circuit, and the size of the fringe capacitance is designed to be much larger than the inner ring capacitance (generally, the capacitance value of the initially set fringe capacitor is in the range of 46.9pF to 71.4pF, The capacitance value of the inner ring capacitor is in the range of 10.7pF ~ 16.05pF, the capacitance value of the edge capacitor is at least 4 times the capacitance value of the inner ring capacitor; the inductance value of the spiral inductor is set to 50nH ~ 500nH), by adopting the form of series connection of internal and external capacitors The structure of the sensor can be simple, the layout is reasonable, and the manufacture is convenient.

As shown in Figure 3, the sensor can be processed by a layered process, which is divided into four layers and processed separately. After each layer of film is processed by photolithography and other processes, it is modified by oxygen ion plasma/ultraviolet treatment, and then the alignment key is carried out. Combined to realize the various components of the planar sensor and the connection structure between them. For example, the second layer and the fourth layer contain metal electrodes, which can be produced by magnetron sputtering + photolithography + electroplating. The material used is Cu, and the thickness of the two metal layers is 5 μm to 10 μm; The first layer, the third layer, and the fourth layer contain microchannels and liquid inlets, which can be made by plasma etching, laser etching and other processes; the planar sensor is finally molded into a curved surface by hot pressing (that is, it is the same as the spherical crown The contact lens matches the curved shape of the contact lens with the IOP sensor.

In the wireless passive intraocular pressure sensor of the present invention, the liquid in the microcavity is discharged into the microchannel by the deformation of the corneal contact lens with the intraocular pressure, which causes the change of the dielectric constant of the inner ring capacitance. Capacitance and inductance form a C-L-C resonant circuit, and the resonant frequency can be detected by an external integrated on the glasses or a frequency-sweeping antenna coil attached to the eye socket, thereby realizing the detection of intraocular pressure. Through the present invention, 24-hour accurate measurement of the intraocular pressure can be realized according to the change of the resonance frequency, and has the characteristics of high sensitivity, large dynamic range, good stability, simple detection and the like. The microcavity among the present invention can also be other shapes except the cylindrical shape as shown in Figure 1 (b), as long as the projection of the center of a plurality of microcavities on the plane where the circular edge of the contact lens is in line with the cornea The circular edge of the contact lens can be evenly distributed on the circumference of the concentric circle, as shown in Fig. 1(a).

The intraocular pressure sensor in the present invention is flexible and is a non-invasive intraocular pressure detection sensor. In the above-described embodiment, the hard layer material of the contact lens is Parylene-c. In addition to Parylene, PC (i.e., Polycarbonate, polycarbonate), PMMA (i.e., polymethylmethacrylate) can also be used. ester, plexiglass) or PET (that is, polyethylene terephthalate); parylene materials can be prepared by chemical vapor deposition processes, and materials such as PMMA, PC, and PET can be prepared by corresponding film manufacturing processes.

Liquid microfluids in the present invention can be liquids with higher dielectric constants such as water and glycerol (from the perspective of microfluidic liquid viscosity, a mixed solution of glycerin and water can also be used), and can also be room temperature ionic liquids, which can form liquid Chemical interface capacitance, electrode/ionic liquid interface capacitance, with extremely high sensitivity.

Those skilled in the art can easily understand that the above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements and improvements made within the spirit and principles of the present invention, All should be included within the protection scope of the present invention.

Claims (8)

1. a kind of non-intrusion type detection of eyeball tension sensor based on micro-fluidic technologies, it is characterised in that including contact lens, spiral shell Inductance, edge capacitance and inner ring electric capacity are revolved, wherein,

The contact lens is in spherical crown shape, and for matchingly being fitted with the eyeball shape of patient when wearing；

The edge capacitance and the spiral inductance are respectively positioned on the contact lens；The spiral inductance is twist distributed, The edge capacitance the contact lens circular edge projection in the plane be located at the spiral inductance at the angle The circular edge of film contact lense helical projection in the plane outside；

The inner ring electric capacity is located on the contact lens, and the inner ring electric capacity is where the circular edge of the contact lens Projection in plane be located at the spiral inductance the contact lens circular edge helical projection in the plane Inside；

One end of the spiral inductance is connected with one end of the edge capacitance, the other end of the spiral inductance and inner ring electricity One end of appearance is connected；The other end of the edge capacitance is connected with the other end of the inner ring electric capacity；

The contact lens is internally provided with cavity and microfluidic channel；The cavity is connected with the microfluidic channel, For depositing fluid, and convey into the microfluidic channel fluid；The amount of the fluid of conveying in the microfluidic channel By Effect of Intraocular Pressure, the capacitance of the inner ring electric capacity becomes with the change of the amount of the fluid conveyed in the microfluidic channel Change；The CLC loops being made up of the edge capacitance, the spiral inductance and the inner ring electric capacity, are realized to the intraocular pressure Detection；

The inner ring electric capacity is capacity plate antenna, and the microfluidic channel is located between two capacitor plates of the capacity plate antenna；

In addition, being somebody's turn to do the non-intrusion type detection of eyeball tension sensor based on micro-fluidic technologies also includes receiving coil, the receiving coil is used The resonant frequency in the CLC loops being made up of in detection the edge capacitance, the spiral inductance and the inner ring electric capacity, and according to The resonant frequency detected judges the size of intraocular pressure.

2. the non-intrusion type detection of eyeball tension sensor as claimed in claim 1 based on micro-fluidic technologies, it is characterised in that the side The capacitance of edge electric capacity is at least 4 times of the inner ring capacitance value；The inductance value of the spiral inductance be 50nH~ 500nH, the capacitance of the edge capacitance is 46.9pF~71.4pF, the capacitance of the inner ring electric capacity for 10.7pF~ 16.05pF。

3. the non-intrusion type detection of eyeball tension sensor as claimed in claim 1 based on micro-fluidic technologies, it is characterised in that the chamber Body is multiple, and this multiple cavities is respectively positioned on the inside of the contact lens, and the center of the cavity is in the contact lens Circular edge in the plane projection along the circle concentric with the circular edge of the contact lens circle distribution.

4. the non-intrusion type detection of eyeball tension sensor as claimed in claim 1 based on micro-fluidic technologies, it is characterised in that the angle The dimensions of film contact lense is set to diameter 13mm~18mm.

5. the non-intrusion type detection of eyeball tension sensor as claimed in claim 1 based on micro-fluidic technologies, it is characterised in that state miniflow The height of body passage is 10 μm~30 μm, and width is 20 μm~80 μm, and total length is 40mm~100mm.

6. the non-intrusion type detection of eyeball tension sensor as claimed in claim 1 based on micro-fluidic technologies, it is characterised in that the stream Body is glycerine, water or ionic liquid at room temperature.

7. the non-intrusion type detection of eyeball tension sensor as claimed in claim 1 based on micro-fluidic technologies, it is characterised in that the angle Film contact lense is formed by stacking by hard layer and soft layer；The soft layer be used for when the contact lens is worn and patient eye Ball is directly contacted, and the soft layer uses PDMS material；The thickness of the hard layer is 60 μm~80 μm, the contact lens Integral thickness is no more than 300 μm；The microfluidic channel, the spiral inductance, the edge capacitance and the inner ring electric capacity are equal In the hard layer, the hard layer is using Parylene, PMMA, PC or PET material.

8. the non-intrusion type detection of eyeball tension sensor as claimed in claim 1 based on micro-fluidic technologies, it is characterised in that the chamber Body is cylindrical, and the tubular height is 80 μm~150 μm, and radius is 0.5mm~1mm.