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WO2022124541A1 - Dispositif de rétine artificielle de type sous-rétinien comprenant des microlentilles et procédé de fabrication associé - Google Patents

Dispositif de rétine artificielle de type sous-rétinien comprenant des microlentilles et procédé de fabrication associé Download PDF

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Publication number
WO2022124541A1
WO2022124541A1 PCT/KR2021/013427 KR2021013427W WO2022124541A1 WO 2022124541 A1 WO2022124541 A1 WO 2022124541A1 KR 2021013427 W KR2021013427 W KR 2021013427W WO 2022124541 A1 WO2022124541 A1 WO 2022124541A1
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Prior art keywords
microlens
sub
type artificial
substrate
artificial retina
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Ceased
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English (en)
Korean (ko)
Inventor
장이운
한의돈
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Cellico Inc
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Cellico Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F9/00—Methods or devices for treatment of the eyes; Devices for putting in contact-lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation

Definitions

  • the present invention relates to a sub-type artificial retina comprising a microlens and a method for manufacturing the same.
  • the retina is an important nervous tissue that converts light entering through the cornea and lens into electrical signals and transmits them to the brain.
  • various retinal diseases occur due to waste products in blood vessels, diseases, and genetic reasons.
  • Retinitis pigmentosa is a progressive retinal degenerative disease caused by dysfunction of photoreceptors distributed in the retina.
  • Age-related macular degeneration is one of the three major blindness diseases, and it is a disease that deteriorates eyesight due to aging and leads to blindness.
  • Artificial retina technology is divided into epi-retina and sub-retinal according to the location where the device is installed (FIG. 1).
  • the device In the epi-type, the device is located in front of the retina and stimulates the ganglion cell layer, and in the sub-type, the device is located in the photoreceptor layer behind the retina and stimulates the bipolar cell layer.
  • image information obtained from an external camera is wirelessly transmitted through an induction coil to the microelectrode array in the eye, and retinal ganglion cells are stimulated.
  • Argus II product from Second Sight, and it is composed of 64 electrode arrays and can control the size of electrical stimulation generated by each electrode.
  • photodiodes and electrical stimulation arrays are located in the photoreceptor cell layer below the retinal cell layer. Photodiodes and electrical stimulation arrays are designed to replace the function of photoreceptors and target bipolar cells as primary electrical stimulation targets.
  • Photodiodes and electrical stimulation arrays are designed to replace the function of photoreceptors and target bipolar cells as primary electrical stimulation targets.
  • France's Pixium Vision's Prima product consists of a 378 pixel electrode array
  • Germany's Retina Implant's Alpha IMS product consists of 1500 photodiode arrays and matching electrode arrays.
  • the photodiode absorbs light to generate a current, and the generated current flows to the electrode and is designed to stimulate retinal neurons.
  • the stimulus array is composed of a pair of one photodiode and one electrode, which means one pixel.
  • this pixel is composed of electrodes, and the photodiode occupies a small area.
  • the current generation efficiency of the photodiode is high, external power can be reduced, the amplification and electrode circuits can be simplified, and it is judged that it can have a significant effect on the miniaturization of the device.
  • an artificial retinal product inserted into the eye ( Figure 2), it consists of a power coil that supplies power, a connecting electrode connected to the circuit, and a stimulation electrode that stimulates photoreceptors.
  • a photodiode is fabricated on the surface of the silicon chip and connected to the stimulation electrode.
  • the pixels are located on the surface of the silicon-based chip, electrodes for stimulation and current movement occupy most of the pixels in one pixel.
  • the electrode (stimulating electrode + connecting electrode) occupies approximately 78% or more, the passivation space made of SiO 2 is about 20%, and the photodiode 1 ⁇ 2% occupies only space in
  • the photodiode is a central part of the artificial retina that receives light and generates an electric current.
  • the area of the photodiode is absolutely small compared to the electrode, and the area of the photodiode is too small to generate a current for cell stimulation, so the CMOS chip amplifies the current to the level of several hundred ⁇ A.
  • a plurality of stimulation electrodes provided on the substrate and generating action potentials to the optic nerve in response to external visual information projected onto the retina;
  • a photodiode array including a plurality of photodiodes disposed on the substrate so as not to contact the stimulation electrode;
  • microlens array including a plurality of microlenses respectively disposed on the plurality of photodiodes
  • the microlens covers the entire photodiode corresponding thereto, and the sub-type artificial retinal apparatus is provided, characterized in that the stimulation electrode is not covered. .
  • preparing a device including a substrate, a stimulation electrode provided on the substrate, and a photodiode disposed on the substrate so as not to contact the stimulation electrode;
  • a method for manufacturing a sub-type artificial retina device comprising a.
  • preparing a device including a substrate, a stimulation electrode provided on the substrate, and a photodiode disposed on the substrate so as not to contact the stimulation electrode;
  • a photoresist in the form of a spherical bead where the microlens is to be located;
  • a method for manufacturing a sub-type artificial retina device comprising a.
  • preparing a device including a substrate, a stimulation electrode provided on the substrate, and a photodiode disposed on the substrate so as not to contact the stimulation electrode;
  • a method for manufacturing a sub-type artificial retina device comprising a.
  • the sub-type artificial retina device provided in one aspect of the present invention has the effect of increasing light collection efficiency, even using a photodiode having the same area, to generate a higher current.
  • FIG. 1 schematically describes the types of artificial retinal devices according to the insertion position of elements in the eyeball
  • Figure 2 schematically shows a cross-section of the artificial retina device inserted into the eyeball
  • 3A to 3D schematically show the trajectory of the light entering through the eyeball hitting the photodiode.
  • 3e is a plan view of an artificial retina device including a microlens according to an embodiment of the present invention.
  • FIG. 4 schematically shows a method for manufacturing an artificial retina device according to an embodiment of the present invention
  • FIG. 5 schematically shows a method of manufacturing an artificial retina device according to another embodiment of the present invention.
  • FIG. 6 schematically shows a method for manufacturing an artificial retina device according to another embodiment of the present invention
  • FIG. 7 shows an image of a microlens manufactured by the method for manufacturing an artificial retina device according to an embodiment of the present invention
  • FIG. 8 is a view showing an image of the microlens according to etching conditions in the microlens manufactured by the method for manufacturing an artificial retina device according to an embodiment of the present invention.
  • a plurality of stimulation electrodes provided on the substrate and generating action potentials to the optic nerve in response to external visual information projected onto the retina;
  • a photodiode array including a plurality of photodiodes disposed on the substrate so as not to contact the stimulation electrode;
  • microlens array including a plurality of microlenses respectively disposed on the plurality of photodiodes
  • the microlens covers the entire photodiode corresponding thereto, and the sub-type artificial retinal apparatus is provided, characterized in that the stimulation electrode is not covered. .
  • the sub-type artificial retina device provided in one aspect of the present invention includes a substrate.
  • the substrate is provided on the retina sub (sub).
  • the sub-type artificial retina device provided in one aspect of the present invention includes a plurality of stimulation electrodes.
  • the stimulation electrode is provided on the substrate.
  • the stimulation electrode generates an action potential to the optic nerve in response to external visual information projected onto the retina.
  • the stimulation electrode generates an action potential toward a corresponding retinal nerve cell in response to a current generated by a photodiode, which will be described later.
  • the sub-type artificial retina device provided in one aspect of the present invention includes a photodiode array including a plurality of photodiodes.
  • the photodiode is disposed so as not to contact the stimulation electrode.
  • the photodiode may be electrically connected to the stimulation electrode through a separate configuration.
  • the photodiode generates current by receiving light in response to external visual information projected onto the retina.
  • Each of the photodiodes corresponds to the stimulation electrode, and one photodiode and one stimulation electrode may form one pixel.
  • the sub-type artificial retina device provided in one aspect of the present invention includes a microlens array including a plurality of microlenses.
  • the microlens is disposed on the photodiode.
  • the microlens is disposed above each photodiode to correspond to each of the plurality of photodiodes.
  • the microlens covers the entire photodiode corresponding thereto, and the stimulation electrode does not.
  • 3E may be an example of the arrangement of such microlenses.
  • looking in a direction perpendicular to the substrate may mean a plane-view of the sub-type artificial retina device as shown in FIG. 3E .
  • the microlens may have a convex shape with a thicker central portion.
  • the cross-sectional area of the microlens may be 1.3 times or more of the cross-sectional area of the photodiode, preferably 1.5 times or more, more preferably 1.8 times or more can
  • the lens can be disposed in an extra space except for the stimulation electrode in one pixel, the cross-sectional area of the photodiode and the microlens does not need to have a 1:1 ratio. .
  • the microlens may be desirable to design the microlens to have a large cross-sectional area as much as possible within a range in which the microlens does not cover the stimulation electrode in order to obtain high light collecting efficiency.
  • FIGS. 3B, 3C, and 3D When comparing FIGS. 3B, 3C, and 3D, it can be seen that the case of FIGS. 3C and 3D having a relatively large cross-sectional area of the microlens has higher light collection efficiency than the case of FIG. 3B having a relatively small cross-sectional area of the microlens.
  • the refractive index of the microlens may exceed 1.33, preferably 1.4 or more, more preferably 1.5 or more. That is, since the refractive index of the eyeball is about 1.33, the refractive index value of the microlens preferably has a value greater than the refractive index of the eyeball.
  • the microlens may include at least one material from the group consisting of a silicon compound and a biocompatible polymer.
  • the silicon compound may include at least one material selected from the group consisting of SiC, SiN and SiO 2 , and the biocompatible polymer is polyimide, perylene C, silicon (Silicone), polymethyl methacrylate (PMMA). ), polyethylene, polydimethylsiloxane (PMDS), polypropylene, polytetrafluoroethylene (PTFE), and polystyrene.
  • the biocompatible polymer is polyimide, perylene C, silicon (Silicone), polymethyl methacrylate (PMMA). ), polyethylene, polydimethylsiloxane (PMDS), polypropylene, polytetrafluoroethylene (PTFE), and polystyrene.
  • the materials are preferable in that they are biocompatible and can perform a passivation role.
  • SiO 2 , SiC and SiN are representative materials capable of performing a passivation role, and are biocompatible materials.
  • the refractive index of SiO 2 is as high as 1.4 to 1.55, whereas the refractive index in the eyeball is 1.33, so that light can be efficiently condensed.
  • the refractive index of SiO 2 is rather low, and for more efficient light collection, the height of the central part of the microlens must be high. can cause
  • SiN reffractive index 1.6 to 2.3
  • SiC about 2.6
  • Figure 3c shows the SiO 2 based microlens structure
  • Figure 3d shows the structure of the SiO 2 lens in which SiC or SiN having a higher refractive index is inserted. can be checked
  • Materials such as polyimide, perylene C, silicone, polymethylmethacrylate, polyethylene, polydimethylsiloxane, polypropylene, polytetrafluoroethylene and polystyrene are also biocompatible polymers and can perform a passivation role, imide is 1.5, perylene C is 1.64, silicone is 1.4 to 1.6, polymethylmethacrylate is 1.49, polyethylene is 1.476, polydimethylsiloxane is 1.4118, polypropylene is 1.596, polytetrafluoroethylene is 1.356, polystyrene is 1.593 Since it has a refractive index of, it can be used as a microlens of the sub-type artificial retinal device provided in one aspect of the present invention.
  • microlens may have a composite structure including both the biocompatible polymer and the silicon compound.
  • the microlens may include a biocompatible polymer layer and a silicon compound layer.
  • the sub-type artificial retina device provided in one aspect of the present invention, high power production can be expected because the area of the photodiode is constant and the light collection efficiency is significantly increased, and at the same time, a passivation function can be performed through a microlens, and biocompatibility. It has the effect of not requiring a separate post-processing for
  • the present invention improves the light collection efficiency without changing the electrode and circuit design, thereby increasing the power production efficiency, thereby lowering the external power consumption and , can contribute to the miniaturization of artificial retina devices by simplifying the amplification circuit.
  • preparing a device including a substrate, a stimulation electrode provided on the substrate, and a photodiode disposed on the substrate so as not to contact the stimulation electrode;
  • a method for manufacturing a sub-type artificial retina device comprising a.
  • the method of manufacturing a sub-type artificial retina device comprises a device including a substrate, a stimulation electrode provided on the substrate, and a photodiode disposed on the substrate so as not to contact the stimulation electrode including preparation steps.
  • the shape of the device can be understood with reference to FIG. 2 .
  • the device may be a CMOS device.
  • the method for manufacturing a sub-type artificial retina device includes depositing a microlens precursor material on the device.
  • the precursor material may be a silicon compound.
  • the method of manufacturing a sub-type artificial retina device includes the step of forming a pattern by applying a photoresist where the microlens is to be located.
  • the microlens covers the entire corresponding photodiode and the stimulation electrode is disposed not to cover, so the photoresist also covers the entire photodiode, A pattern should be formed so as not to cover the stimulation electrode.
  • the method for manufacturing a sub-type artificial retina device includes annealing the photoresist at a temperature below its melting point.
  • the photoresist When the photoresist is annealed at a temperature below the melting point of the photoresist, the photoresist has a convex shape like a convex lens.
  • the method for manufacturing a sub-type artificial retina device provided in another aspect of the present invention includes forming a convex microlens by performing etching.
  • the microlens precursor material in the portion where the photoresist is not applied is removed, and the microlens precursor material under the photoresist has a convex lens shape according to the photoresist shape having a convex shape by annealing. .
  • the manufacturing method of the sub-type artificial retina device provided in another aspect of the present invention can be understood in more detail with reference to FIG. 4 .
  • preparing a device including a substrate, a stimulation electrode provided on the substrate, and a photodiode disposed on the substrate so as not to contact the stimulation electrode;
  • a photoresist in the form of a spherical bead where the microlens is to be located;
  • a method for manufacturing a sub-type artificial retina device comprising a.
  • the steps of preparing the device and depositing the microlens precursor material are the same as those described above, and thus will not be repeated.
  • the microlens precursor material may be a silicon compound.
  • a method of manufacturing a sub-type artificial retina device includes disposing a photoresist in the form of a spherical bead where the microlens is to be positioned.
  • a convex shape is made by annealing the photoresist at a temperature below the melting point
  • the sub-type artificial retina device provided in another aspect of the present invention is By disposing the photoresist sheet in the form of a spherical bead from the beginning, the microlens precursor material under the photoresist may have a convex lens shape during subsequent etching.
  • the manufacturing method of the sub-type artificial retina device provided in another aspect of the present invention can be understood in more detail with reference to FIG. 7 .
  • microlenses having various shapes can be obtained according to etching conditions as shown in FIG. 8 .
  • preparing a device including a substrate, a stimulation electrode provided on the substrate, and a photodiode disposed on the substrate so as not to contact the stimulation electrode;
  • a method for manufacturing a sub-type artificial retina device comprising a.
  • the steps of preparing a device, depositing a microlens precursor material, and applying a photoresist to form a pattern are the same as described above. , will not be repeated.
  • the microlens precursor material may be a biocompatible polymer.
  • a method of manufacturing a sub-type artificial retina device includes the steps of forming a pattern of a microlens precursor material according to the pattern by performing etching, and performing etching to form a microlens precursor material according to the pattern. forming a pattern.
  • the method for manufacturing a sub-type artificial retina device includes annealing the microlens precursor material at a temperature below a melting point to form a convex microlens.
  • the microlens precursor material When the annealing is performed at a temperature below the melting point of the microlens precursor material, the microlens precursor material has a convex shape and is manufactured as a microlens.
  • the manufacturing method of the sub-type artificial retina device provided in another aspect of the present invention can be understood in more detail with reference to FIG. 5 .
  • the method of manufacturing a sub-type artificial retina device provided in another aspect of the present invention may further include depositing a silicon compound layer on the formed microlens.
  • the silicon compound layer may be formed to have a curvature according to the surface of the microlens.
  • a convex shape through annealing of a photoresist or use of a spherical bead-shaped photoresist of microlens can be obtained, and in the case of manufacturing a biocompatible polymer-based microlens, a convex microlens can be obtained by annealing the biocompatible polymer.
  • SiO 2 , SiC, and SiN used as a passivation layer in a CMOS chip were manufactured in the form of a lens as shown in FIG. 4 .
  • a photodiode was fabricated on a Si substrate, and then a device having a connecting electrode and a stimulating electrode positioned thereon was prepared.
  • the photoresist was annealed at a temperature below the melting point of the photoresist (100 to 200° C.) to make the photoresist in a semicircular shape, and then etched (FIG. 4D). As a result, a convex shape as shown in FIG. 4E A microlens was formed on top of the photodiode.
  • a biocompatible polymer such as polymethyl methacrylate, polyethylene, polydimethylsiloxane, polypropylene, polytetrafluoroethylene and polystyrene was prepared in the form of a lens as shown in FIG. 5 .
  • a photodiode was fabricated on a Si substrate, and then a device having a connecting electrode and a stimulating electrode positioned thereon was prepared.
  • a liquid polymer was coated thereon with a microlens precursor material, and then, a photoresist used as a mask layer was applied to the position where the microlens was to be formed to form a pattern (FIG. 5). C).
  • the coating of the liquid polymer may be performed by spin coating or deposition.
  • SiO 2 , SiC, and SiN layers were additionally deposited on the microlens prepared in Example 2 (FIG. 6).
  • the silicon compound layer may be formed to have a curvature according to the surface of the microlens.

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Abstract

Est divulgué un dispositif de rétine artificielle de type sous-rétinien qui comporte : un substrat disposé sur une zone sous-rétinienne ; une pluralité d'électrodes de stimulation disposées sur le substrat et générant des potentiels d'action sur des nerfs optiques en réponse à des informations visuelles externes, projetées sur une rétine ; un réseau de photodiodes comprenant une pluralité de photodiodes disposées sur le substrat de façon à ne pas entrer en contact avec les électrodes de stimulation ; un réseau de microlentilles comprenant une pluralité de microlentilles disposées respectivement sur la pluralité de photodiodes. Lorsque le dispositif de rétine artificielle de type sous-rétinien est vu dans une direction perpendiculaire au substrat, la microlentille recouvre toutes les photodiodes correspondant à cette dernière mais ne recouvre pas les électrodes de stimulation. Bien qu'un dispositif de rétine artificielle de type sous-rétinien présenté selon un aspect de la présente invention utilise une photodiode ayant la même zone, le dispositif de rétine artificielle de type sous-rétinien a pour effet d'augmenter l'efficacité de captage de la lumière pour ainsi générer un courant plus important.
PCT/KR2021/013427 2020-12-10 2021-09-30 Dispositif de rétine artificielle de type sous-rétinien comprenant des microlentilles et procédé de fabrication associé Ceased WO2022124541A1 (fr)

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KR102514572B1 (ko) * 2022-10-18 2023-03-28 주식회사 셀리코 안구 이식형 초소형 자극기 및 이의 제조방법
KR102531735B1 (ko) * 2022-12-27 2023-05-12 주식회사 셀리코 초소형 자극기 및 이의 제조방법

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KR101838150B1 (ko) 2016-08-31 2018-03-15 가천대학교 산학협력단 광센서 어레이 기반의 서브형 인공망막 장치 및 인공망막 장치의 구동 방법

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JP2012517272A (ja) * 2009-02-09 2012-08-02 ナノレチナ，インコーポレーテッド 網膜人工器官（ｒｅｔｉｎａｌｐｒｏｓｔｈｅｓｉｓ）
KR20180008929A (ko) * 2010-10-27 2018-01-24 이리듐 메디칼 테크놀로지 컴퍼니 리미티드 플렉시블 인조 망막 장치들
KR20190053511A (ko) * 2017-11-10 2019-05-20 서울대학교산학협력단 Cop 또는 coc를 사용한 인공망막 장치
KR20190066856A (ko) * 2017-12-06 2019-06-14 재단법인대구경북과학기술원 풍선 타입 망막 자극장치 및 이의 제조방법
KR102133288B1 (ko) * 2019-02-19 2020-07-14 재단법인대구경북과학기술원 3차원 전극장치의 제조방법 및 이의 제조방법으로 제조된 3차원 전극장치

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