CN115376391A - Three-dimensional eyeball imitation body and preparation method and application thereof - Google Patents

Three-dimensional eyeball imitation body and preparation method and application thereof Download PDF

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CN115376391A
CN115376391A CN202210998045.7A CN202210998045A CN115376391A CN 115376391 A CN115376391 A CN 115376391A CN 202210998045 A CN202210998045 A CN 202210998045A CN 115376391 A CN115376391 A CN 115376391A
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layer
eyeball
optical
retina
dimensional
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马东奇
申书伟
孙明斋
徐晓嵘
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Suzhou Institute Of Higher Studies University Of Science And Technology Of China
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Suzhou Institute Of Higher Studies University Of Science And Technology Of China
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    • GPHYSICS
    • G09EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09BEDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/28Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B32LAYERED PRODUCTS
    • B32BLAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00Layered products comprising a layer of synthetic resin
    • B32B27/06Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material
    • B32B27/08Layered products comprising a layer of synthetic resin as the main or only constituent of a layer, which is next to another layer of the same or of a different material of synthetic resin
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B32LAYERED PRODUCTS
    • B32BLAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00Layered products comprising a layer of synthetic resin
    • B32B27/18Layered products comprising a layer of synthetic resin characterised by the use of special additives
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B32LAYERED PRODUCTS
    • B32BLAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B27/00Layered products comprising a layer of synthetic resin
    • B32B27/28Layered products comprising a layer of synthetic resin comprising synthetic resins not wholly covered by any one of the sub-groups B32B27/30 - B32B27/42
    • B32B27/283Layered products comprising a layer of synthetic resin comprising synthetic resins not wholly covered by any one of the sub-groups B32B27/30 - B32B27/42 comprising polysiloxanes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B32LAYERED PRODUCTS
    • B32BLAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B7/00Layered products characterised by the relation between layers; Layered products characterised by the relative orientation of features between layers, or by the relative values of a measurable parameter between layers, i.e. products comprising layers having different physical, chemical or physicochemical properties; Layered products characterised by the interconnection of layers
    • B32B7/04Interconnection of layers
    • B32B7/12Interconnection of layers using interposed adhesives or interposed materials with bonding properties
    • GPHYSICS
    • G09EDUCATION; CRYPTOGRAPHY; DISPLAY; ADVERTISING; SEALS
    • G09BEDUCATIONAL OR DEMONSTRATION APPLIANCES; APPLIANCES FOR TEACHING, OR COMMUNICATING WITH, THE BLIND, DEAF OR MUTE; MODELS; PLANETARIA; GLOBES; MAPS; DIAGRAMS
    • G09B23/00Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes
    • G09B23/28Models for scientific, medical, or mathematical purposes, e.g. full-sized devices for demonstration purposes for medicine
    • G09B23/30Anatomical models
    • G09B23/32Anatomical models with moving parts
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B32LAYERED PRODUCTS
    • B32BLAYERED PRODUCTS, i.e. PRODUCTS BUILT-UP OF STRATA OF FLAT OR NON-FLAT, e.g. CELLULAR OR HONEYCOMB, FORM
    • B32B2535/00Medical equipment, e.g. bandage, prostheses, catheter

Abstract

The invention discloses a three-dimensional eyeball imitation body and a preparation method and application thereof, the three-dimensional eyeball imitation body comprises a vitreous body and a lower eyeball wall which are assembled together, the lower eyeball wall at least comprises a retina layer, the retina layer is provided with retina veins, the retina layer contains an optical parameter adjusting reagent for simulating the optical parameters of a retina, the preparation process comprises the steps of respectively preparing the vitreous body and the lower eyeball wall, and then assembling the vitreous body and the lower eyeball wall together. The three-dimensional eyeball imitation prepared by the invention has the three-dimensional structure and functional characteristics closer to the eyeball, and the eyeball imitation can be made into a multifunctional, multi-modal and multi-scale structure according to the requirements.

Description

Three-dimensional eyeball imitation body and preparation method and application thereof
Technical Field
The invention belongs to the technical field of biological imitations, and particularly relates to a multifunctional, multi-modal and multi-scale three-dimensional eyeball imitator as well as a preparation method and application thereof.
Background
Most systemic or cerebral diseases, such as hypertension, diabetes, stroke, etc., cause changes in the internal structure of the eyeball. The use of noninvasive imaging devices such as ultrasound, CT, MRI, which are commonly used in clinical practice, can diagnose many ophthalmic diseases (glaucoma, age-related macular degeneration, etc.) by detecting changes in the tissues inside the eyeball, and can also help to assess sub-clinical or clinical changes of many systemic diseases, thereby assisting in the optimization of treatment regimens. Furthermore, the transparent structure of the eye allows optical (near infrared, visible light) or photoacoustic devices to directly make noninvasive observations and diagnoses thereof.
However, these non-invasive detection apparatuses including ultrasound, CT, MRI, fundus camera, OCT, photoacoustic detection systems have non-uniform reference performance due to differences in device processing and parameter drift over time, resulting in differences between detection results. In order to ensure the stability and comparability of the detection result and promote the development of clinical application based on noninvasive detection equipment, a traceable calibration device capable of simulating the characteristics of the structure, the optics, the ray transmittance and the like of the eyeball must be developed. In order to achieve calibration better, the traceable calibration device not only needs to be capable of simulating the characteristics of a normal eyeball, but also needs to be capable of correlating physiological and pathological characteristics of related pathological changes of the eyeball. The use of such devices to simulate pathological features including ocular pressure abnormalities to calibrate and calibrate medical examination equipment is also critical to improving the reliability and stability of the examination.
At present, bio-optical imitators that can simulate the structure and functional characteristics of human body have become one of the best traceable standards recognized in the academic and commercial industries. Meanwhile, many two-dimensional eyeball imitations and three-dimensional eyeball imitations based on liquid materials and shells have been developed, but at present, the performances of the eyeball imitations are far from those of real tissues, for example, physiological and pathological parameters of real eyeballs cannot be well correlated. Therefore, there is a need for a multifunctional, multi-modal, multi-scale three-dimensional eyeball imitation and a preparation method and application thereof.
Disclosure of Invention
Aiming at the existing technical problems, the invention provides a multifunctional, multi-modal and multi-scale three-dimensional eyeball imitation body, a preparation method and application thereof, which can be flexibly adjusted to simulate most physiological and pathological characteristics including the optical characteristics of the retina of a real human body, the three-dimensional vascular morphological structure and the blood oxygen saturation, and the prepared eyeball imitation body not only can provide accurate calibration for single-modal image equipment and help the registration between multi-modal image equipment, but also can be used for developing a simulation model of eyeball injury caused by pathological changes and the like, thereby facilitating the observation of doctors.
The technical scheme of the invention is as follows:
the invention provides a three-dimensional eyeball imitator, which comprises a vitreous body and a lower eyeball wall which are assembled together, wherein the lower eyeball wall at least comprises a retina layer, the retina layer is provided with a retina venation, and the retina layer contains an optical parameter adjusting reagent for simulating optical parameters of a retina.
Preferably, the glass body is a solid structure made of optical materials, optical parameters of the glass body are similar to those of an actual glass body, and the solid structure can be integrally and uniformly prepared or prepared layer by layer in a gradual change mode according to requirements in the preparation process.
Preferably, the vitreous body is a hollow structure made of optical materials, a reserved cavity is arranged in the vitreous body, the vitreous body is further provided with a perfusion inlet and a perfusion outlet which are communicated with the reserved cavity, a preparation solution simulating human eye fluid is perfused in the reserved cavity or is filled with a filling material, the preparation solution can be also called vitreous body fluid, is semisolid and colloidal, the main component of the preparation solution is water, and the filling material can be selected from high polymer materials, glass or gel.
Preferably, the outer side of the retina layer is provided with a choroid layer containing an optical parameter modifying agent for mimicking an optical parameter of the choroid.
Preferably, a scleral layer is arranged outside the choroid layer, and the scleral layer contains an optical parameter adjusting agent for simulating the optical parameters of the sclera.
Preferably, the outer side of the scleral layer is provided with an anterior boundary layer, and the anterior boundary layer contains an optical parameter adjusting reagent for simulating the optical parameters of the anterior boundary layer.
Preferably, the outer side of the anterior limiting membrane layer is provided with a corneal epithelial layer, and the corneal epithelial layer contains an optical parameter adjusting agent for simulating the optical parameters of the anterior limiting membrane.
In practical application, the lower eyeball wall with different membrane layer numbers of structural and functional parameters is optimized and customized according to requirements, for example, when the membrane layer number is 2, a choroid layer is designed on the outer side of a retina, when the membrane layer number is 3, a scleral layer is also designed on the outer side of the choroid layer, when the membrane layer number is 4, an anterior boundary layer is also designed on the outer side of the scleral layer, and when the membrane layer number is 5, a corneal epithelium layer is also designed on the outer side of the anterior boundary layer; each film layer is made of corresponding optical materials doped with optical parameter adjusting reagents, wherein the optical materials comprise but are not limited to polydimethylsiloxane, glass and gel, and the optical parameter adjusting reagents comprise but are not limited to titanium dioxide, silicon dioxide, aluminum oxide, indian ink and graphite.
Preferably, the three-dimensional eyeball imitation body further comprises an upper eyeball wall, the vitreous body is positioned in a cavity formed by splicing the upper eyeball wall and the lower eyeball wall, and the upper eyeball wall is made of an optical material. Upper eye wall processing methods include, but are not limited to, spin coating, casting, and 3D printing. In practical applications, only the lower eyeball wall can be selected, or the upper eyeball wall and the lower eyeball wall can be selected simultaneously, and the upper eyeball wall is installed after the vitreous body and the lower eyeball wall are assembled together.
The invention also provides a preparation method of the three-dimensional eyeball imitation body, which comprises the following steps:
s1, preparing a glass body based on an optical material;
s2, preparing a lower eyeball wall at least comprising a retina layer;
wherein the preparation process of the retina layer comprises the following steps: and modeling based on the obtained retina choroid structure of the real human eye to obtain a retina model of the human eye, and processing the retina model obtained based on the modeling by using an optical material doped with an optical parameter adjusting reagent to obtain the retina layer with the retina choroid. The data of the retina choroid structure of a real human eye is obtained based on images or anatomy, the processing method of the retina layer comprises but is not limited to spin coating, pouring and 3D printing, when the spin coating method is adopted, a silicon wafer with the retina choroid is obtained by means of photoetching, etching, laser ablation or 3D printing, then the optical material doped with the optical parameter adjusting reagent is used for spin coating on the silicon wafer with the retina choroid, and after solidification, the coating is scraped off to obtain the retina layer with the retina choroid.
And S3, assembling the vitreous body and the lower eyeball wall together to form the three-dimensional eyeball imitative body.
Preferably, in the step S2, after preparing the retina layers, according to the number n of the layers of the lower eye wall, 2 ≦ n ≦ 5, the first n-1 layers are selectively prepared in the order of the choroid layers (selectable layer), the scleral layers (selectable layer), the anterior boundary layer (selectable layer) and the corneal epithelium layer (selectable layer);
the preparation process of the choroid layer comprises the following steps: doping an optical material by using an optical parameter adjusting reagent, adjusting the absorption and scattering coefficients of the optical material to simulate the optical parameters of the choroid, and then processing the optical material after doping to prepare the choroid layer; methods of processing include, but are not limited to, spin coating, casting, and 3D printing;
the scleral layer preparation process comprises: doping an optical material by using an optical parameter adjusting reagent, adjusting the absorption and scattering coefficients of the optical material to simulate the optical parameters of the sclera, and then processing the doped optical material to prepare the scleral layer; methods of processing include, but are not limited to, spin coating, casting, and 3D printing;
the preparation process of the front boundary film layer comprises the following steps: doping an optical material by using an optical parameter adjusting reagent, adjusting the absorption and scattering coefficients of the optical material to simulate the optical parameters of the front boundary film, and then processing the doped optical material to prepare a front boundary film layer; methods of processing therein include, but are not limited to, spin coating, casting, and 3D printing, preferably spin coating;
the preparation process of the corneal epithelium layer comprises the following steps: the optical material is doped with an optical parameter adjusting agent to adjust the absorption and scattering coefficients thereof so as to simulate the optical parameters of the corneal epithelium, and then the doped optical material is processed to obtain the corneal epithelium, wherein the processing method comprises but is not limited to spin coating, pouring and 3D printing, and preferably the spin coating.
For example, when n is 2, the number of layers representing the lower eye wall is 2, including the retina layer and the choroid layer, and in this case, the choroid layer is prepared according to the above preparation process; when n is 3, the number of the layers representing the lower eye wall is 3, including the retina layer, the choroid layer and the scleral layer, and at this time, the choroid layer and the scleral layer are prepared according to the preparation process; when n is 4, the number of the layers representing the lower eye wall is 4, including the retina layer, the choroid layer, the scleral layer and the anterior boundary layer, and at this time, the choroid layer, the scleral layer and the anterior boundary layer are prepared according to the preparation process; when n is 5, the number of layers representing the lower eye wall is 5, including the retina, choroid, sclera, anterior boundary and corneal epithelium, and the choroid, sclera, anterior boundary and corneal epithelium are prepared according to the above preparation process.
The thicknesses of the anterior boundary membrane layer and the corneal epithelial layer are very small, the model disclosed by the invention supports the requirements of different scenes, and eyeball models with different modes are manufactured according to different required precisions. In general, this high precision is not required, and since the epithelial cell layer is about 50um thick, both layers are not formed, but if necessary, they can be assembled, and the corresponding processing method is preferably spin coating.
Preferably, in the step S2, according to the number n of the layers of the lower eye wall, where n is greater than or equal to 2 and less than or equal to 5, the first n layers are selected and assembled from the retina layer, the choroid layer, the scleral layer, the anterior boundary layer and the corneal epithelial layer in the order from inside to outside to form the lower eye wall. Specifically, when n is 2, the retina layer and the choroid layer are assembled; when n is 3, assembling the retina layer, the choroid layer and the sclera layer; when n is 4, assembling the retina layer, the choroid layer, the scleral layer and the anterior boundary layer; when n is 5, the retinal layer, the choroid layer, the scleral layer, the anterior boundary layer and the corneal epithelial layer are assembled. The assembling method includes, but is not limited to, bonding based on a thermoplastic stretchable adhesive, surface modification, heating, etc., and bonding with a thermoplastic stretchable adhesive is further preferred.
The method for assembling the lower eyeball wall and the vitreous body includes but is not limited to thermal processing, mechanical processing, laser ablation, adhesive, heat shrinkable film, ion bonding and the like, and the vitreous body and the lower eyeball wall are bonded together by preferably adopting thermoplastic stretchable adhesive and then are shrunk by the shrinkable film to complete the assembly;
wherein the thermoplastic stretchable adhesive includes, but is not limited to, styrene-ethylene-butylene-styrene copolymer SEBS.
The three-dimensional eyeball imitation body is applied to the accurate calibration of the performance and parameters of single-mode imaging equipment and the registration among multi-mode imaging equipment.
Specifically, the blood oxygen calibration device based on the three-dimensional eyeball imitator comprises the three-dimensional eyeball imitator, an eyeground camera and a blood perfusion device;
the blood perfusion device is used for performing blood oxygen perfusion on retina veins of the three-dimensional eyeball imitations and comprises a first peristaltic pump, and a circulation inlet pipe and a circulation outlet pipe are connected between the first peristaltic pump and the retina veins;
the fundus camera captures a two-wavelength image of a three-dimensional eyeball phantom during perfusion.
The three-dimensional eyeball imitation body is applied to an eyeball injury simulation device. The prepared eyeball imitations are related to physiological and pathological parameters, and can also provide an eye substitute for ophthalmic surgeons to observe simulated injuries.
The damage simulation device comprises the three-dimensional eyeball imitation body and a second peristaltic pump, wherein the preparation solution for simulating human eye liquid is filled into the reserved cavity, and a connecting pipe is connected between the second peristaltic pump and a filling inlet of the glass structure.
The beneficial effects of the invention are:
1) The three-dimensional eyeball imitation body prepared by the invention has a three-dimensional structure and functional characteristics which are closer to eyeballs, and the eyeball imitation body can be made into a multifunctional, multi-modal and multi-scale structure according to requirements, so that the eyeball structure, optical characteristics, blood oxygen, blood flow and other functional characteristics under normal and pathological states can be simulated more truly;
2) The eyeball phantom can not only accurately calibrate the performance and parameters (including but not limited to parameters such as resolution, blood oxygen saturation, reflectivity, transmissivity and absorptivity) of the ophthalmic imaging equipment, but also help the registration among multi-mode imaging equipment, and can be used for developing a simulation model of eyeball injury caused by ophthalmic lesions and other reasons, so that doctors can observe the condition conveniently;
3) Each layer of eye mask of the lower eye wall of the eyeball imitation body is manufactured respectively, parameters such as the optical parameters, the structures and the like of different film layers can be adjusted in a personalized mode, even if one film layer is damaged, the use of other film layers is not influenced, and the performance stability and the reusability of the eyeball imitation body are improved;
4) The three-dimensional eyeball imitation body prepared by the invention has simple composition and low cost, can easily realize batch production and is convenient to popularize.
Drawings
The invention is further described below with reference to the following figures and examples:
FIG. 1 is a schematic structural diagram of a three-dimensional eyeball analogue;
FIG. 2 is a schematic view of the retinal choroid;
FIG. 3 is a structural component view of a first lower eye wall;
FIG. 4 is a structural composition diagram of a second lower eye wall;
FIG. 5 is a structural composition diagram of a third lower eye wall;
fig. 6 is a schematic structural diagram of a blood oxygen calibration device based on a three-dimensional eyeball phantom.
The labels in fig. 1 to 5 are: 1. a glass body; 2. a lower eye wall; 21. a retinal layer; 211. the retinal choroid; 22. the choroid layer; 23. a scleral layer; 24. a front boundary film layer; 25. a corneal epithelial layer; 3. the wall of the eyeball.
The labels in fig. 6 are: 4. a three-dimensional eyeball imitative body; 5. an eye fundus camera; 6. a blood perfusion device.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the accompanying drawings in combination with the embodiments. It should be understood that the description is intended to be exemplary only, and is not intended to limit the scope of the present invention. Moreover, in the following description, descriptions of well-known structures and techniques are omitted so as to not unnecessarily obscure the concepts of the present invention.
Example 1
As shown in fig. 1 and 2, a three-dimensional eyeball phantom comprises a vitreous body 1 and a lower eyeball wall 2 which are assembled together, wherein the lower eyeball wall 2 at least comprises a retina layer 21, in practical application, the lower eyeball wall 2 with different layers of structural and functional parameters can be optimized and customized according to requirements, each layer is respectively made of corresponding optical materials doped with optical parameter adjusting agents, as shown in fig. 3, the lower eyeball wall 2 only comprises the retina layer 21, as shown in fig. 4, the lower eyeball wall 2 comprises the retina layer 21, a choroid layer 22 and a scleral layer 23 which are sequentially arranged from inside to outside, as shown in fig. 5, the lower eyeball wall 2 comprises the retina layer 21, the choroid layer 22, the scleral layer 23, a front boundary layer 24 and a corneal epithelium layer 25 which are sequentially arranged from inside to outside.
The three-dimensional eyeball imitation body also comprises an upper eyeball wall 3, the vitreous body 1 is positioned in a cavity formed by splicing the upper eyeball wall 3 and the lower eyeball wall 2, and the upper eyeball wall 3 is made of polydimethylsiloxane silica. In practical applications, only the lower eyeball wall 2 may be selected, or both the upper eyeball wall 3 and the lower eyeball wall 2 may be selected, and the upper eyeball wall 3 is mounted after the vitreous body 1 and the lower eyeball wall 2 are assembled together. In addition, a corresponding fixing support portion for supporting the three-dimensional eyeball analogue can be further provided as required.
The vitreous body 1 can be a solid structure made of polydimethylsiloxane, optical parameters of the vitreous body 1 are similar to those of the actual vitreous body 1, the vitreous body 1 can also be a hollow structure made of polydimethylsiloxane, a reserved cavity is arranged in the vitreous body 1, the vitreous body 1 is also provided with a perfusion inlet and a perfusion outlet which are communicated with the reserved cavity, a preparation solution simulating human eye fluid is perfused in the reserved cavity or is filled with a filling material, the preparation solution is also called vitreous body fluid, the main components of the preparation solution are water (accounting for 99 percent) and colloid, the main structural components of the colloid are collagen in a fine fiber mesh support and hyaluronan interwoven between the collagen and the hyaluronic acid, and the filling material can be a high molecular material, glass or gel.
Retina layers 21 are provided with retina choroid 211, retina layers 21 comprise optical parameter adjusting agents for simulating optical parameters of the retina, choroid layers 22 comprise optical parameter adjusting agents for simulating optical parameters of the choroid, sclera layers 23 comprise optical parameter adjusting agents for simulating optical parameters of the sclera, anterior interface layers 24 comprise optical parameter adjusting agents for simulating optical parameters of the anterior interface, and corneal epithelium layers 25 comprise optical parameter adjusting agents for simulating optical parameters of the corneal epithelium; the above-mentioned film layers are respectively made of optical materials doped with optical parameter regulating agents, including but not limited to polydimethylsiloxane, glass and gel, and the optical parameter regulating agents include but not limited to titanium dioxide, silicon dioxide, aluminum oxide, indian ink and graphite, preferably titanium dioxide and indian ink.
Example 2
As shown in fig. 6, a blood oxygen calibration device based on a three-dimensional eyeball phantom comprises a three-dimensional eyeball phantom 4, an eyeground camera 5 and a blood perfusion device 6; the blood perfusion device 6 is used for performing blood oxygen perfusion on the retina venation 211 of the three-dimensional eyeball phantom, the blood perfusion device 6 comprises a first peristaltic pump, and a circulation inlet pipe and a circulation outlet pipe are connected between the first peristaltic pump and the retina venation 211; the fundus camera 5 captures a two-wavelength image of the three-dimensional eye phantom 4 during perfusion.
The preparation process of the three-dimensional eyeball imitation body adopted by the calibration device comprises the following steps:
1) Firstly, preparing a spherical solid glass body 1 structure by using PDMS (polydimethylsiloxane) in a pouring mode, wherein the PDMS has good light transmittance, and constructing a lower eyeball wall 2 structure by using the PDMS as a substrate;
2) Acquiring a retina choroid 211 structure of a real human eye through an image acquired by a fundus camera, acquiring a retina model of the human eye through modeling, and photoetching the silicon wafer based on the retina model acquired through modeling to acquire the silicon wafer with the retina choroid;
the Indian ink and titanium dioxide are used for doping PDMS, curing agents are added, and absorption and scattering coefficients of the curing agents are adjusted to simulate optical parameters of a retina; using the doped PDMS to spin-coat on a silicon wafer with the retina venation, and scraping the coating with a knife after the coating is solidified to obtain the retina layer 21 with the retina venation 211;
3) Doping PDMS with India ink and titanium dioxide, adjusting the absorption and scattering coefficients of the PDMS to simulate optical parameters of the choroid, then performing spin coating on a corresponding silicon wafer by using the doped PDMS, and scraping the coating by using a knife after the coating is solidified to obtain a choroid layer 22;
4) Doping PDMS with India ink and titanium dioxide, adjusting the absorption and scattering coefficients of the PDMS to simulate optical parameters of a sclera, then carrying out spin coating on a corresponding silicon wafer by using the doped PDMS, and scraping off a coating by using a knife after curing to obtain a scleral layer 23;
5) Concentrically arranged retina layers 21, choroid layers 22 and sclera layers 23 are bonded together by SEBS (styrene-ethylene-butylene-styrene thermoplastic stretchable adhesive) to form a lower eye wall 2, wherein the retina layers 21, the choroid layers 22 and the sclera layers 23 are distributed in the order from inside to outside; the lower eye wall 2 is constructed as shown in fig. 4;
6) And coating the SEBS on the glass body 1, coating the SEBS on the innermost layer of the lower eyeball wall 2, bonding the glass body 1 and the lower eyeball wall 2 together, and then shrinking through a shrink film to complete assembly.
The method for calibrating blood oxygen by using the blood oxygen calibration device based on the three-dimensional eyeball imitations has the advantages that the retina venation 211 forms a micro-channel and can support blood oxygen perfusion, and the method comprises the following steps:
1) Performing blood oxygen perfusion on the retina venation 211 of the three-dimensional eyeball imitations through the blood perfusion device 6, and circulating different blood oxygen Saturation (SO) degrees by utilizing the blood perfusion device 6 and the retina venation 211 2 ) A horizontal Red Blood Cell (RBC) solution;
wherein the three-dimensional eyeball imitation body is fixed by a bracket at the chin bracket of the eyeground camera 5;
2) Capturing two-wavelength images of a three-dimensional eyeball phantom with the fundus camera 5 during perfusion, continuously taking three sets of images at each oxygenation level, and then calculating ODRcor values of the retinal veins 211 by the ODRcor values and the corresponding blood oxygen Saturation (SO) 2 ) Obtaining calibration parameters by linear fitting; the ratio of Optical Densities (ODs) is ODR (ODR = OD) 600 /OD 569 ) At O in 2 Sensitivity and O 2 Images of the vessels were recorded at insensitive wavelengths (600 and 569nm, respectively) and during fractionated hypoxia the OD ratio (ODR) was compared with the systemic SO 2 In a negative linear relationship. This is a non-invasive measurement of Hb O in retinal blood vessels by digital imaging 2 Degree of Saturation (SO) 2 ) The method of (1).
Example 3
The utility model provides a damage analogue means based on three-dimensional eyeball is imitative body, includes three-dimensional eyeball and imitates the body, still includes the second peristaltic pump, is connected with the connecting pipe between the import of infusing of second peristaltic pump and glass structure.
Glaucoma is the result of damage to the optic nerve, which is usually associated with elevated intraocular pressure, with a significant reduction in the outflow of aqueous humor from a patient, but with the production of aqueous humor remaining unchanged, and an imbalance in aqueous humor outflow and production directly leads to elevated intraocular pressure. According to the pathological cause of glaucoma, the three-dimensional eyeball imitative body adopts a cavity type design, correspondingly, the vitreous body is provided with a reserved cavity, and is also provided with a perfusion inlet and a perfusion outlet which are communicated with the reserved cavity, and the reserved cavity is filled with a preparation solution simulating eye drops of a human eye. In use, the perfusion outlet is specifically adjusted and the size of the perfusion outlet is controlled to simulate a reduction in aqueous humor drainage.
The preparation process of the three-dimensional eyeball imitation body in the injury simulation device comprises the following steps:
1) The glass body adopts a cavity type design, the eyeball is modeled, the material PDMS is used, the light transmittance of the PDMS is good, a cavity of the glass body 1 with a perfusion inlet and a perfusion outlet is directly obtained by adopting 3D printing, and the glass bodies with different perfusion outlet sizes are printed according to equal proportion;
2) Mixing PDMS (polydimethylsiloxane), titanium dioxide and India ink in proportion, adding a curing agent, and carrying out spin coating on a silicon wafer with the retinal vein 211 by using a spin coater to obtain a retinal layer 21 with the retinal vein 211; the lower eye wall 2 of this embodiment comprises only the retinal layer 21, as shown in fig. 3
3) The retina layer 21 and the glass body 1 with the perfusion opening are assembled by an adhesive SEBS. According to the liquid components of the real human eyes, the solution is prepared to simulate the eye liquid of the human eyes, and the eye liquid can be poured into the simulated cavity of the vitreous body.
The three-dimensional eye phantom of the embodiment does not have a choroid layer 22 and a scleral layer 23 and is used for simulating the influence of intraocular pressure rise on retina, and the method for performing injury simulation by using the device comprises the following steps: the eyeball imitator is filled by the second peristaltic pump, the filled liquid is a preparation solution for simulating human eye liquid, the filling rate is adjusted, and due to the reduction of the filling outlet, the liquid cannot be discharged in time and the increase of the filling rate can cause the increase of intraocular pressure, so that the eyeball imitator can be used for observing the influence of the increase of the intraocular pressure on a retina by a surgeon, and calibration can also be provided for a medical instrument.
It should be understood that the above-described embodiments of the present invention are merely illustrative of or explaining the principles of the invention and are not to be construed as limiting the invention. Therefore, any modification, equivalent replacement, improvement and the like made without departing from the spirit and scope of the present invention should be included in the protection scope of the present invention. Further, it is intended that the appended claims cover all such variations and modifications as fall within the scope and boundaries of the appended claims or the equivalents of such scope and boundaries.

Claims (12)

1. A three-dimensional eyeball analogue which is characterized by comprising a vitreous body and a lower eyeball wall which are assembled together, wherein the lower eyeball wall at least comprises a retina layer, the retina layer is provided with retina veins, and the retina layer contains an optical parameter adjusting agent for simulating optical parameters of a retina.
2. The three-dimensional biomimetic globe according to claim 1, wherein the vitreous body is a solid structure made of optical material.
3. The three-dimensional eyeball phantom according to the claim 1, characterized in that the vitreous body is a hollow structure made of optical material, a reserved cavity is arranged in the vitreous body, the vitreous body is also provided with a perfusion inlet and a perfusion outlet which are communicated with the reserved cavity, and the reserved cavity is filled with a preparation solution simulating the human eye fluid or filled with a filling material.
4. The three-dimensional biomimetic according to claim 1, wherein a choroid layer is disposed outside of the retinal layer, the choroid layer comprising optical parameter modifying agents for simulating optical parameters of the choroid.
5. The three-dimensional eyeball analogue of claim 4, wherein a scleral layer is arranged outside the choroid layer, and the scleral layer contains an optical parameter adjusting agent for simulating the optical parameters of the sclera.
6. The three-dimensional eyeball prosthesis of claim 5, wherein an anterior boundary membrane layer is arranged outside the scleral layer, and the anterior boundary membrane layer contains an optical parameter adjusting reagent for simulating the optical parameters of the anterior boundary membrane.
7. The three-dimensional eyeball phantom according to claim 6, wherein the outer side of the anterior boundary membrane layer is provided with a corneal epithelial layer, and the corneal epithelial layer contains an optical parameter adjusting agent for simulating the optical parameters of the anterior boundary membrane.
8. The three-dimensional eyeball analog according to claim 1, which is characterized in that the three-dimensional eyeball analog further comprises an upper eyeball wall, the vitreous body is positioned in a cavity formed by the combination of the upper eyeball wall and the lower eyeball wall, and the upper eyeball wall is made of optical material.
9. A preparation method of a three-dimensional eyeball imitation body is characterized by comprising the following steps:
s1, preparing a glass body based on an optical material;
s2, preparing a lower eyeball wall at least comprising a retina layer;
the preparation process of the retina layer comprises the following steps: modeling based on the obtained retina choroid structure of the real human eye to obtain a retina model of the human eye, and processing the retina model obtained by modeling to obtain the retina layer with the retina choroid by using the optical material doped with the optical parameter adjusting reagent.
And S3, assembling the vitreous body and the lower eyeball wall together to form the three-dimensional eyeball imitative body.
10. The method for preparing a three-dimensional eyeball analogue as claimed in claim 9, wherein in the step S2, after preparing the retina layers, according to the number n of the layers of the lower eyeball wall, n is more than or equal to 2 and less than or equal to 5, the first n-1 layers are selected and prepared according to the sequence of the choroid layers, the scleral layers, the anterior boundary layers and the corneal epithelium layers;
the preparation process of the choroid layer comprises the following steps: doping an optical material by using an optical parameter adjusting reagent, adjusting the absorption and scattering coefficients of the optical material to simulate the optical parameters of the choroid, and then processing the optical material after doping to prepare the choroid layer;
the scleral layer preparation process comprises: doping an optical material by using an optical parameter adjusting reagent, adjusting the absorption and scattering coefficients of the optical material to simulate the optical parameters of the sclera, and then processing the doped optical material to prepare the scleral layer;
the preparation process of the front boundary film layer comprises the following steps: doping an optical material by using an optical parameter adjusting reagent, adjusting the absorption and scattering coefficients of the optical material to simulate the optical parameters of the front boundary film, and then processing the doped optical material to prepare a front boundary film layer;
the preparation process of the corneal epithelium layer comprises the following steps: optical parameters adjusting agents are used for doping optical materials, absorption and scattering coefficients of the optical materials are adjusted to simulate optical parameters of corneal epithelium, and then the doped optical materials are used for processing to obtain the corneal epithelium.
11. The method for preparing a three-dimensional eyeball analogue as claimed in claim 10, wherein in the step S2, according to the number n of the layers of the lower eyeball wall, n is more than or equal to 2 and less than or equal to 5, the first n layers are selected and assembled from the retina layer, the choroid layer, the scleral layer, the anterior boundary layer and the corneal epithelium layer in the sequence from inside to outside to form the lower eyeball wall.
12. Use of the three-dimensional eye phantom according to any one of claims 1-8 for accurate calibration of single modality imaging device performance and parameters and registration between multi-modality imaging devices, or for use in an eye injury simulation apparatus.
CN202210998045.7A 2022-08-19 2022-08-19 Three-dimensional eyeball imitation body and preparation method and application thereof Pending CN115376391A (en)

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