技术领域technical field
本实用新型涉及一种功能化植入式柔性电极，特别涉及具有可通过触发形成电流的功能层的功能化植入式柔性电极，属于生物材料技术领域。The utility model relates to a functionalized implantable flexible electrode, in particular to a functionalized implanted flexible electrode with a functional layer capable of forming current through triggering, and belongs to the technical field of biomaterials.
背景技术Background technique
随着生活节奏的不断加快，由于人们身心经常处于高度紧张的状态，使得视网膜色素炎、黄斑病变、抑郁症、癫痫等神经系统疾病日益增多。与此同时，全球老龄化更是加剧了神经性疾病概率，并成为一大社会负担。With the continuous acceleration of the pace of life, because people are often in a state of high physical and mental tension, neurological diseases such as retinitis pigmentosa, macular degeneration, depression, and epilepsy are increasing day by day. At the same time, global aging has exacerbated the probability of neurological diseases and become a major social burden.
通过穿戴或植入式的神经电刺激疗法的迅速发展，和神经假体的出现为广大的患者带来了新的希望。神经电刺激疗法是一种在不破坏神经组织的前提下通过调节神经进行治疗方法，它可以起到治疗或部分恢复神经功能的作用。由于该方法具有安全、微创等特点，并且，对于某些特殊的神经系统疾病来说，如心脏起搏器、人工耳蜗和人造视网膜等，确是无可替代的方法，目前已经成功应用于临床。The rapid development of wearable or implantable nerve electrical stimulation therapy and the emergence of neural prosthesis have brought new hope to the majority of patients. Nerve electrical stimulation therapy is a treatment method that regulates nerves without destroying nerve tissue, and it can treat or partially restore nerve function. Because the method is safe and minimally invasive, and it is an irreplaceable method for some special neurological diseases, such as cardiac pacemakers, cochlear implants and artificial retinas, etc., it has been successfully applied to clinical.
随着新技术的不断创新和发展，如今更多的神经电刺激假体已经逐渐走向应用，正在为患有帕金森症、癫痫、运动神经障碍、中风、抑郁症等疾病的人带来新的希望。神经假体将帮助神经损伤患者实现受损神经功能的修复和重建，改善其生活质量。伴随着治疗神经性疾病的社会需求，功能化电子器件的研究和发展已经成为医疗产业和全社会的客观要求。With the continuous innovation and development of new technologies, more neural electrical stimulation prostheses have gradually been applied, and are bringing new hope to people suffering from Parkinson's disease, epilepsy, motor nerve disorder, stroke, depression and other diseases . Neuroprosthetics will help patients with nerve injuries to repair and reconstruct damaged nerve functions and improve their quality of life. Along with the social demand for the treatment of neurological diseases, the research and development of functional electronic devices has become an objective requirement of the medical industry and the whole society.
虽然目前神经假体的研究正在快速进展，但至今尚只有植入式心脏起博器、人工耳蜗、人造视网膜等为数不多的植入式神经假体进入临床应用。目前这个领域的工作正面临很多科学技术难题带来的挑战，其中最大的困难之一就是长期植入可靠性、有效性及稳定性。拿人造视网膜假体来说，由于现有电极还是通过传统方法设计，不具备特殊功能，无法解决手术高风险、管状视野、生物相容性，以及植入后有效性、稳定性与可靠性差等重大问题。例如神经电极的生物相容性问题，生物相容性差的神经电极植入人体可能会损害多个组织部分，包括毛细血管、细胞外基质和细胞。另外，巨噬细胞会聚集到植入的电极周围，将植入体包裹。小胶质细胞随后被激活，然后分泌活性氧物质以及炎性细胞因子，其中一些因子具有毒性，因此其邻近神经元可能被损害，严重影响神经电极的性能，无法满足长期植入的目的。Although the research on neural prosthesis is progressing rapidly, only a few implantable neural prostheses, such as implantable cardiac pacemakers, cochlear implants, and artificial retinas, have entered clinical applications so far. The current work in this field is facing challenges brought about by many scientific and technological problems, one of the biggest difficulties is long-term implant reliability, effectiveness and stability. Taking the artificial retinal prosthesis as an example, because the existing electrodes are still designed by traditional methods and do not have special functions, they cannot solve the problems of high surgical risk, tubular vision, biocompatibility, poor effectiveness, stability and reliability after implantation, etc. major problem. For example, the biocompatibility of neural electrodes, implantation of poorly biocompatible neural electrodes in the human body may damage multiple tissue parts, including capillaries, extracellular matrix, and cells. In addition, macrophages will gather around the implanted electrodes, enveloping the implant. Microglia are then activated, and then secrete reactive oxygen species and inflammatory cytokines, some of which are toxic, so their adjacent neurons may be damaged, which seriously affects the performance of nerve electrodes and cannot meet the purpose of long-term implantation.
实用新型内容Utility model content
为解决上述技术问题，本实用新型的主要目的在于提供一种新的功能化植入式柔性电极，以期能解决目前神经假体长期植入的有效性、稳定性、可靠性问题中的一个或多个。In order to solve the above-mentioned technical problems, the main purpose of this utility model is to provide a new functionalized implantable flexible electrode, in order to solve one or more of the problems of the effectiveness, stability and reliability of the long-term implantation of neural prostheses. Multiple.
本实用新型的另一目的在于提供含上述功能化植入式柔性电极的微电极阵列及相应的神经假体。Another object of the present invention is to provide a micro-electrode array containing the above-mentioned functionalized implantable flexible electrodes and a corresponding neural prosthesis.
为实现上述目的，一方面，本实用新型提供一种功能化植入式柔性电极，其至少包括能产生电流或电压的功能层。To achieve the above object, on the one hand, the utility model provides a functionalized implantable flexible electrode, which at least includes a functional layer capable of generating current or voltage.
本实用新型提供的是一种全新的电极，其至少包括上述功能层，在此基础上，还可以包括基底层以及进一步的导电层。这个电极可以通过将基底层与功能层复合得到，基底层提供支撑，功能层提供电流或电压；该电极也可以是将功能层耦合设计到带有基底层和导电层的传统电极上而得到的，这样电极就不需要外界电源功能，通过功能层即可提供电流或电压以实现刺激效果。The utility model provides a brand-new electrode, which at least includes the above-mentioned functional layer, and on this basis, may also include a base layer and a further conductive layer. This electrode can be obtained by combining the base layer with the functional layer, the base layer provides support, and the functional layer provides current or voltage; the electrode can also be obtained by coupling the functional layer to a conventional electrode with a base layer and a conductive layer , so that the electrode does not need an external power supply function, and can provide current or voltage through the functional layer to achieve the stimulation effect.
在本实用新型提供的功能化植入式柔性电极中，优选地，所述功能层能够通过光、电、磁、声、热和力中的一种或两种以上的方式的触发而产生电流或电压。本实用新型设置可通过光、电、磁、声、热、力等触发形成电流或电压的功能层，使得本实用新型的柔性电极无需复杂的线路连接和器件封装，即可实现神经刺激器件的功能，不仅极大降低了手术风险，长期植入安全性风险，更是拓展了神经刺激器件的应用领域。In the functionalized implantable flexible electrode provided by the present invention, preferably, the functional layer can be triggered by one or more of light, electricity, magnetism, sound, heat and force to generate current or voltage. The utility model is provided with a functional layer that can be triggered by light, electricity, magnetism, sound, heat, force, etc. to form a current or voltage, so that the flexible electrode of the utility model can realize the function of the nerve stimulation device without complex line connection and device packaging. The function not only greatly reduces the risk of surgery and the risk of long-term implantation safety, but also expands the application field of nerve stimulation devices.
在一些实施方式中，功能层的材料包括场效应晶体管、发光二极管、光电二极管、光电材料、压电材料和磁电材料等中的一种或两种以上的组合。优选地，功能层的材料包括光电材料、导电材料、磁电材料和超声波与光致形变材料中的一种或两种以上的组合。其中，光电材料包括砷化镓、铜铟镓硒、碲化镉、钙钛矿、染料敏化材料、CIGS材料、光电有机材料、光电高分子材料、聚偏氟乙烯、聚三氟氯乙烯、聚三氟乙烯、压电陶瓷、Cr2O3、Ti2O3中的一种或两种以上的组合；导电材料包括铂、金、铂铱合金、银、镁、氮化钛、氧化铱、铟锡氧化物、镓铟合金、镓铟锡合金、石墨烯、碳纳米管、导电高分子材料及其它们的复合物中的一种或两种以上的组合，优选地，上述导电高分子材料包括聚吡咯、聚苯硫醚、聚对苯撑、聚苯胺、聚噻吩及它们的衍生物中的一种或两种以上的组合；磁电材料包括GaFeO3、LiCoPO4、TbPO4、REMnO3、REMn2O5、TbMn2O5、BiFeO3、BaTiO3、Pb(Zr,Ti)O3、(1-x)[Pb(Mg1/3Nb2/3)O3]-x[PbTiO3](PMN-PT，其中X为0.1-0.9)中的一种或两种以上的组合；超声波与光致形变材料包括螺吡喃、二芳烯、萘并吡喃、偶氮苯及它们的聚合物和衍生物中的一种或两种以上的组合。In some embodiments, the material of the functional layer includes one or a combination of two or more of field effect transistors, light emitting diodes, photodiodes, photoelectric materials, piezoelectric materials, and magnetoelectric materials. Preferably, the material of the functional layer includes one or a combination of two or more of photoelectric materials, conductive materials, magnetoelectric materials, and ultrasonic and photodeformable materials. Among them, optoelectronic materials include gallium arsenide, copper indium gallium selenide, cadmium telluride, perovskite, dye-sensitized materials, CIGS materials, optoelectronic organic materials, optoelectronic polymer materials, polyvinylidene fluoride, polychlorotrifluoroethylene, One or more combinations of polytrifluoroethylene, piezoelectric ceramics, Cr2 O3 , Ti2 O3 ; conductive materials include platinum, gold, platinum-iridium alloy, silver, magnesium, titanium nitride, iridium oxide , indium tin oxide, gallium indium alloy, gallium indium tin alloy, graphene, carbon nanotubes, conductive polymer materials and their composites, or a combination of two or more, preferably, the above conductive polymer Materials include polypyrrole, polyphenylene sulfide, polyparaphenylene, polyaniline, polythiophene and their derivatives, or a combination of two or more; magnetoelectric materials include GaFeO3 , LiCoPO4 , TbPO4 , REMnO3. REMn2 O5 , TbMn2 O5 , BiFeO3 , BaTiO3 , Pb(Zr,Ti)O3 , (1-x)[Pb(Mg1/3 Nb2/3 )O3 ]-x[ PbTiO3 ] (PMN-PT, where X is 0.1-0.9) or a combination of two or more; ultrasonic and photodeformable materials include spiropyran, diarylene, naphthopyran, azobenzene and One or a combination of two or more of their polymers and derivatives.
在一些实施方式中，本实用新型的功能化植入式柔性电极可以由刺激端、引线部分、功能端组成；其中，刺激端包括基底层(或称刺激端基底层)、导电层以及设置于导电层表面的刺激位点，导电层位于基底层的表面；功能端包括基底层(或称功能端基底层，不同于刺激端的基底层)和功能层。在该结构中，刺激端和功能端通过引线部分连接在一起，功能层在光、电、磁、声、热和力等的触发下产生电流或电压，并通过引线部分传递到刺激端，通过刺激端的刺激位点来实现相应的刺激功能。In some embodiments, the functionalized implantable flexible electrode of the present utility model can be composed of a stimulating end, a lead part, and a functional end; wherein, the stimulating end includes a base layer (or called a stimulating end base layer), a conductive layer, and a The stimulation site on the surface of the conductive layer, the conductive layer is located on the surface of the basal layer; the functional end includes the basal layer (or the basal layer at the functional end, which is different from the basal layer at the stimulating end) and the functional layer. In this structure, the stimulating end and the functional end are connected together through the lead part, and the functional layer generates current or voltage under the trigger of light, electricity, magnetism, sound, heat and force, etc., and transmits it to the stimulating end through the lead part. The stimulation site on the stimulation end realizes the corresponding stimulation function.
在一些实施方式中，该功能化植入式柔性电极由耦合有功能层的刺激端组成，即功能层与刺激端的各个层复合在一起，具体可以有以下两种结构(但不限于此)：In some embodiments, the functionalized implantable flexible electrode is composed of a stimulating end coupled with a functional layer, that is, the functional layer is combined with each layer of the stimulating end. Specifically, there may be the following two structures (but not limited thereto):
第一种结构：刺激端包括基底层、导电层以及设置于导电层表面的刺激位点，功能层位于基底层的表面或者嵌入基底层之中(例如将功能材料与基底层材料复合在一起制成兼具基底功能和功能材料相应功能的基底层)，导电层位于功能层的表面或者嵌有功能层的基底层的表面：在这种结构下，功能层实际上可以同时起到引线的作用，将其在光、电、磁、声、热和力等的触发下产生电流或电压传递到各个刺激位点。The first type of structure: the stimulation end includes a base layer, a conductive layer, and a stimulation site arranged on the surface of the conductive layer, and the functional layer is located on the surface of the base layer or embedded in the base layer (for example, the functional material and the base layer material are compounded together to make In this structure, the functional layer can actually act as a lead at the same time. , under the triggering of light, electricity, magnetism, sound, heat and force, etc., it generates current or voltage and transmits it to each stimulation site.
第二种结构：刺激端包括两层基底层、导电层和功能层，导电层位于两层基底层之间，功能层位于顶部的基底层的表面：在这种结构下，功能层在在光、电、磁、声、热和力等的触发下产生电流或电压，并通过中间的导电层传递到各个刺激位点。The second structure: the stimulation end includes two base layers, a conductive layer and a functional layer, the conductive layer is located between the two base layers, and the functional layer is located on the surface of the top base layer: under this structure, the functional layer is Under the triggering of , electricity, magnetism, sound, heat and force, etc., current or voltage is generated and transmitted to each stimulation site through the middle conductive layer.
本实用新型还可以对前述功能化植入式柔性电极进行修饰进一步提供具有相应功能的柔性电极，修饰的方法包括在电极表面的电化学修饰、生物材料修饰，以及电极背面的高分子材料修饰等。通过在电极表面进行电化学修饰，能够降低电极表面阻抗、提升刺激效率。The utility model can also modify the aforementioned functionalized implantable flexible electrodes to further provide flexible electrodes with corresponding functions. The modification methods include electrochemical modification on the electrode surface, biological material modification, and polymer material modification on the back of the electrode, etc. . By performing electrochemical modification on the electrode surface, the electrode surface impedance can be reduced and the stimulation efficiency can be improved.
在一些实施方式中，在电极的刺激端的刺激位点上设有电镀层，该电镀层的材料包括无机材料、导电高分子材料或它们的复合材料中的一种或两种以上的组合。In some embodiments, an electroplating layer is provided on the stimulating site of the stimulating end of the electrode, and the material of the electroplating layer includes one or a combination of two or more of inorganic materials, conductive polymer materials, or composite materials thereof.
在一些实施方式中，所述电镀层的无机材料包括碳纳米管、石墨烯、钛、铂、铑、钯、铱、金和铌等中的一种或两种以上的组合。In some embodiments, the inorganic material of the electroplating layer includes one or a combination of two or more of carbon nanotubes, graphene, titanium, platinum, rhodium, palladium, iridium, gold, and niobium.
在一些实施方式中，所述电镀层的有机高分子材料包括聚离子液体、聚吡咯、聚苯硫醚、聚对苯撑、聚苯胺、聚噻吩、水凝胶和它们的衍生物中的一种或两种以上的组合。In some embodiments, the organic polymer material of the electroplating layer includes one of polyionic liquid, polypyrrole, polyphenylene sulfide, polyparaphenylene, polyaniline, polythiophene, hydrogel and their derivatives. one or a combination of two or more.
在一些实施方式中，所述电镀层的形貌为微结构，所述微结构包括微颗粒、微柱、微针、微片、微孔、微管、微线、微锥结构或两种以上的微结构的复合结构或其多级复合结构。在一些实施方式中，所述微结构的厚度例如为20nm-200μm。在一些实施方式中，所述微颗粒(粒径)、微柱(长度)、微针(长度)、微片(长度)、微孔(孔径)、微管(管径)、微线(长度)、微锥(轴向长度)结构的尺寸可以控制为1nm-20μm。In some embodiments, the morphology of the electroplated layer is a microstructure, and the microstructure includes microparticles, micropillars, microneedles, microplates, microholes, microtubes, microwires, microcone structures or two or more The composite structure of the microstructure or its multi-level composite structure. In some embodiments, the thickness of the microstructure is, for example, 20 nm-200 μm. In some embodiments, the microparticle (particle size), microcolumn (length), microneedle (length), microplatelet (length), micropore (aperture), microtube (diameter), microwire (length) ), the size of the microcone (axial length) structure can be controlled to 1nm-20μm.
在一些实施方式中，所述电极刺激位点上可以修饰有生物材料层，生物材料通过分子层面设计如分子氢键、范德华力、亲疏水作用、静电作用，通过物理或化学方法将其修饰到柔性电极上，所述生物材料层的材料包括多肽、蛋白、水凝胶和它们的复合物中的一种或者两种以上的组合，所述生物材料层的厚度优选可以为1nm-50μm。通过在电极表面进行生物材料修饰，能够确保植入式柔性电极植入后的生物相容性，防止长期植入的免疫反应。In some embodiments, the electrode stimulation site can be modified with a biomaterial layer, and the biomaterial can be modified to On the flexible electrode, the material of the biomaterial layer includes one or a combination of two or more of polypeptides, proteins, hydrogels and their complexes, and the thickness of the biomaterial layer can preferably be 1 nm-50 μm. Biomaterial modification on the electrode surface can ensure the biocompatibility of the implantable flexible electrode after implantation and prevent long-term implanted immune response.
在一些生物材料层中，所述水凝胶可以包括由如下材料形成的水凝胶：聚(N-异丙基丙烯酰胺)、聚(N-正丙基丙烯酰胺)、聚(N-环丙基丙烯酰胺)、聚(N-异丙基甲基丙烯酰胺)、蛋白、聚(N-乙基丙烯酰胺)、聚(N-丙烯酰氧基-N-丙基哌嗪)、聚(N-(L)-(1-羟甲基)丙基甲基丙烯酰胺)、聚[N-(2-甲基丙烯酰氧乙基)吡咯烷酮]、聚[N-(3-丙烯酰氧丙基)吡咯烷酮]、聚[N-(3-甲基丙烯酰氧丙基)吡咯烷酮]、聚[N-(2-丙烯酰氧丙基)吡咯烷酮]、聚[N-(1-甲基-2-丙烯酰氧乙基)吡咯烷酮]、聚(2-烷基-2-唑啉)、聚(2-乙基-2-唑啉)、聚(2-异丙基-2-唑啉)、聚(2-正丙基-2-唑啉)、聚甲基丙烯酸二甲氨乙酯、聚(N-乙烯基环己内酰胺)、聚丙烯酰吡咯烷、聚甲基乙烯基醚、聚甲氧基乙基乙烯基醚、聚乙氧基乙基乙烯基醚、聚乙氧基乙氧基乙烯基醚、聚环氧丙烷、聚(低聚(乙二醇)单甲醚甲基丙烯酸酯)、聚有机膦腈、弹性蛋白样多肽、琼脂糖、聚乙烯醇、壳聚糖、淀粉、聚丙烯酰胺、聚乙烯吡咯烷酮、透明质酸、透明质酸钠、聚苯乙烯磺酸钠、聚对苯乙烯磺酸、聚甲基丙烯酸羟乙酯、聚乙二醇、聚丁二醇、聚乙二醇甲基丙烯酸酯、聚乙二醇丙烯酸酯、基质胶、明胶、海藻酸、胶原、聚L-赖氨酸、聚L-谷胺酸、羟丙基甲基纤维素、羟乙基纤维素、羧甲基纤维素、羧乙烯聚合物、卡拉胶、玻尿酸、聚乙烯醇、聚甲基丙烯酸甲酯、聚甲基丙烯酸乙酯、聚甲基丙烯酸叔丁基酯、聚丙烯酸甲酯、聚丙烯酸乙酯、聚乙烯基吡啶、聚丙烯酸、聚L-谷氨酸、聚组氨酸、聚天冬氨酸、聚[(2-二甲基氨基)甲基丙烯酸乙酯]、聚甲基丙烯酸、聚乙基丙烯酸、聚丙基丙烯酸、聚乙烯基苯甲酸、聚衣康酸、聚乙二醇丙烯酸酯磷酸、聚乙二醇甲基丙烯酸酯磷酸、聚乙烯磷酸、聚(4-乙烯基-苯基磷酸)、聚乙烯磺酸、聚(4-苯乙烯磺酸)、聚乙烯苯硼酸、聚甲基丙烯酸二甲氨基乙酯、聚甲基丙烯酸二乙氨基乙酯、聚(N-乙基吡咯烷甲基丙烯酸酯)聚合物和它们的共聚物中的一种或两种以上的组合。In some biomaterial layers, the hydrogel may comprise a hydrogel formed from poly(N-isopropylacrylamide), poly(N-n-propylacrylamide), poly(N-cyclo Propylacrylamide), poly(N-isopropylmethacrylamide), protein, poly(N-ethylacrylamide), poly(N-acryloyloxy-N-propylpiperazine), poly( N-(L)-(1-hydroxymethyl)propyl methacrylamide), poly[N-(2-methacryloyloxyethyl)pyrrolidone], poly[N-(3-acryloyloxypropyl base) pyrrolidone], poly[N-(3-methacryloxypropyl)pyrrolidone], poly[N-(2-acryloyloxypropyl)pyrrolidone], poly[N-(1-methyl-2 -acryloyloxyethyl)pyrrolidone], poly(2-alkyl-2-oxazoline), poly(2-ethyl-2-oxazoline), poly(2-isopropyl-2-oxazoline), Poly(2-n-propyl-2-oxazoline), polydimethylaminoethyl methacrylate, poly(N-vinyl cyclocaprolactam), polyacryloylpyrrolidine, polymethyl vinyl ether, polymethoxy Ethyl ethyl vinyl ether, polyethoxy ethyl vinyl ether, polyethoxy ethoxy vinyl ether, polypropylene oxide, poly(oligo(ethylene glycol) monomethyl ether methacrylate) , polyorganophosphazene, elastin-like polypeptide, agarose, polyvinyl alcohol, chitosan, starch, polyacrylamide, polyvinylpyrrolidone, hyaluronic acid, sodium hyaluronate, sodium polystyrene sulfonate, polypara Styrene Sulfonic Acid, Polyhydroxyethyl Methacrylate, Polyethylene Glycol, Polytetramethylene Glycol, Polyethylene Glycol Methacrylate, Polyethylene Glycol Acrylate, Matrigel, Gelatin, Alginic Acid, Collagen, Polyethylene Glycol L-lysine, poly-L-glutamic acid, hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, carboxyvinyl polymer, carrageenan, hyaluronic acid, polyvinyl alcohol, polymethyl Methyl acrylate, polyethyl methacrylate, poly-tert-butyl methacrylate, polymethyl acrylate, polyethyl acrylate, polyvinylpyridine, polyacrylic acid, poly-L-glutamic acid, polyhistidine, Polyaspartic acid, poly[(2-dimethylamino)ethyl methacrylate], polymethacrylic acid, polyethylacrylic acid, polypropylacrylic acid, polyvinylbenzoic acid, polyitaconic acid, polyethylene Glycol acrylate phosphoric acid, polyethylene glycol methacrylate phosphoric acid, polyvinyl phosphoric acid, poly(4-vinyl-phenyl phosphoric acid), polyvinyl sulfonic acid, poly(4-styrene sulfonic acid), polyvinyl benzene One or more of boric acid, polydimethylaminoethyl methacrylate, polydiethylaminoethyl methacrylate, poly(N-ethylpyrrolidine methacrylate) polymers and their copolymers The combination.
在一些实施方式中，生物材料层中可以含有抗炎药，所述抗炎药例如包括地塞米松、强的松、保泰松和抗炎性多肽中的一种或两种以上的组合。生物材料层中含有抗炎药可使本实用新型柔性电极具有抗炎功能，从而使得所述柔性电极能长期植入。In some embodiments, the biomaterial layer may contain anti-inflammatory drugs, such as one or a combination of two or more of dexamethasone, prednisone, phenylbutazone, and anti-inflammatory polypeptides. The anti-inflammatory drug contained in the biomaterial layer can make the flexible electrode of the present invention have an anti-inflammatory function, so that the flexible electrode can be implanted for a long time.
在一些实施方式中，在所述功能化植入式柔性电极的背面可以修饰有高分子材料层。在本实用新型电极背面修饰上高分子材料层，可使柔性电极具备形状适应性改变功能化，这既可以实现微创方式植入，还可以确保电极植入后能有效匹配生物体组织，提高刺激有效性；再者这还可以实现电极宽幅设计，增加刺激区域面积，拓展神经刺激功能，解决人造视网膜管状视野技术难题。所述高分子材料层的材料可以包括聚(N-异丙基丙烯酰胺)、聚(N-正丙基丙烯酰胺)、聚(N-环丙基丙烯酰胺)、聚(N-异丙基甲基丙烯酰胺)、聚(N-乙基丙烯酰胺)、聚(N-丙烯酰氧基-N-丙基哌嗪)、聚(N-(L)-(1-羟甲基)丙基甲基丙烯酰胺)、聚[N-(2-甲基丙烯酰氧乙基)吡咯烷酮]、聚[N-(3-丙烯酰氧丙基)吡咯烷酮]、聚[N-(3-甲基丙烯酰氧丙基)吡咯烷酮]、聚[N-(2-丙烯酰氧丙基)吡咯烷酮]、聚[N-(1-甲基-2-丙烯酰氧乙基)吡咯烷酮]、聚(2-烷基-2-唑啉)、聚(2-乙基-2-唑啉)、聚(2-异丙基-2-唑啉)、聚(2-正丙基-2-唑啉)、聚甲基丙烯酸二甲氨乙酯、聚(N-乙烯基环己内酰胺)、聚丙烯酰吡咯烷、聚甲基乙烯基醚、聚甲氧基乙基乙烯基醚、聚乙氧基乙基乙烯基醚、聚乙氧基乙氧基乙烯基醚、聚环氧丙烷、聚(低聚(乙二醇)单甲醚甲基丙烯酸酯)、聚有机膦腈、蛋白、弹性蛋白样多肽、琼脂糖、聚乙烯醇、壳聚糖、淀粉、聚丙烯酰胺、聚乙烯吡咯烷酮、透明质酸、透明质酸钠、聚苯乙烯磺酸钠、聚对苯乙烯磺酸、聚甲基丙烯酸羟乙酯、聚乙二醇、聚丁二醇、聚乙二醇甲基丙烯酸酯、聚乙二醇丙烯酸酯、基质胶、明胶、海藻酸、胶原、聚L-赖氨酸、聚L-谷胺酸、羟丙基甲基纤维素、羟乙基纤维素、羧甲基纤维素、羧乙烯聚合物、卡拉胶、玻尿酸、聚乙烯醇、聚甲基丙烯酸甲酯、聚甲基丙烯酸乙酯、聚甲基丙烯酸叔丁基酯、聚丙烯酸甲酯、聚丙烯酸乙酯、聚乙烯基吡啶、聚碳酸酯、聚酰亚胺、醋酸纤维素、尼龙、聚(乙烯基对苯二甲酸酯)、聚磷腈、全氟磺酸、聚乙烯、聚苯乙烯、酚醛树脂、聚丙烯酸、聚L-谷氨酸、聚组氨酸、聚天冬氨酸、聚[(2-二甲基氨基)甲基丙烯酸乙酯]、聚甲基丙烯酸、聚乙基丙烯酸、聚丙基丙烯酸、聚乙烯基苯甲酸、聚衣康酸、聚乙二醇丙烯酸酯磷酸、聚乙二醇甲基丙烯酸酯磷酸、聚乙烯磷酸、聚(4-乙烯基-苯基磷酸)、聚乙烯磺酸、聚(4-苯乙烯磺酸)、聚乙烯苯硼酸、聚甲基丙烯酸二甲氨基乙酯、聚甲基丙烯酸二乙氨基乙酯、聚(N-乙基吡咯烷甲基丙烯酸酯)、聚(2-乙烯基吡啶)、聚(N-丙烯酰基-N-烯基哌嗪)、聚丙烯酰吗啉、聚(4-乙烯基吡啶)、聚乙烯亚胺树状大分子、聚乙烯醇、预氧化丙烯腈、聚氨酯、环氧树脂、乙烯-醋酸乙烯酯共聚物、聚酰亚胺、聚己内酯、聚吡咯烷酮、聚多巴胺、弹性蛋白多肽@黑鳞纳米颗粒复合水凝胶、聚乳酸、聚乙醇酸、聚乳酸-羟基乙酸共聚物材料和它们的衍生物中的一种或两种以上的组合。In some embodiments, the back of the functionalized implantable flexible electrode can be decorated with a polymer material layer. The polymer material layer is modified on the back of the electrode of the utility model, so that the flexible electrode can be functionalized with shape adaptability, which can not only realize minimally invasive implantation, but also ensure that the electrode can effectively match the biological tissue after implantation, and improve Stimulation effectiveness; moreover, this can also realize the electrode wide design, increase the area of the stimulation area, expand the nerve stimulation function, and solve the technical problem of artificial retinal tubular vision. The material of the polymer material layer may include poly(N-isopropylacrylamide), poly(N-n-propylacrylamide), poly(N-cyclopropylacrylamide), poly(N-isopropylacrylamide), methacrylamide), poly(N-ethylacrylamide), poly(N-acryloyloxy-N-propylpiperazine), poly(N-(L)-(1-hydroxymethyl)propyl Methacrylamide), poly[N-(2-methacryloyloxyethyl)pyrrolidone], poly[N-(3-acryloyloxypropyl)pyrrolidone], poly[N-(3-methylpropylene Acyloxypropyl)pyrrolidone], poly[N-(2-acryloyloxypropyl)pyrrolidone], poly[N-(1-methyl-2-acryloyloxyethyl)pyrrolidone], poly(2-alkane base-2-oxazoline), poly(2-ethyl-2-oxazoline), poly(2-isopropyl-2-oxazoline), poly(2-n-propyl-2-oxazoline), poly Dimethylaminoethyl methacrylate, poly(N-vinyl cyclocaprolactam), polyacryloylpyrrolidine, polymethyl vinyl ether, polymethoxyethyl vinyl ether, polyethoxyethyl vinyl Ether, polyethoxyethoxyvinyl ether, polypropylene oxide, poly(oligo(ethylene glycol) monomethyl ether methacrylate), polyorganophosphazene, protein, elastin-like polypeptide, agarose , polyvinyl alcohol, chitosan, starch, polyacrylamide, polyvinylpyrrolidone, hyaluronic acid, sodium hyaluronate, sodium polystyrene sulfonate, polystyrene sulfonic acid, polyhydroxyethyl methacrylate, Polyethylene glycol, polytetramethylene glycol, polyethylene glycol methacrylate, polyethylene glycol acrylate, Matrigel, gelatin, alginic acid, collagen, poly-L-lysine, poly-L-glutamic acid, Hydroxypropyl methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, carboxyvinyl polymer, carrageenan, hyaluronic acid, polyvinyl alcohol, polymethyl methacrylate, polyethyl methacrylate, polymethylmethacrylate tert-butyl acrylate, polymethyl acrylate, polyethyl acrylate, polyvinylpyridine, polycarbonate, polyimide, cellulose acetate, nylon, poly(vinyl terephthalate), poly Phosphazene, perfluorosulfonic acid, polyethylene, polystyrene, phenolic resin, polyacrylic acid, poly-L-glutamic acid, polyhistidine, polyaspartic acid, poly[(2-dimethylamino)formaldehyde ethyl acrylate], polymethacrylic acid, polyethylacrylic acid, polypropylacrylic acid, polyvinylbenzoic acid, polyitaconic acid, polyethylene glycol acrylate phosphoric acid, polyethylene glycol methacrylate phosphoric acid, poly Vinyl phosphoric acid, poly(4-vinyl-phenyl phosphoric acid), polyvinyl sulfonic acid, poly(4-styrene sulfonic acid), polyvinyl phenylboronic acid, polydimethylaminoethyl methacrylate, polymethacrylic acid di Ethylaminoethyl ester, poly(N-ethylpyrrolidine methacrylate), poly(2-vinylpyridine), poly(N-acryloyl-N-alkenylpiperazine), polyacryloylmorpholine, poly (4-vinylpyridine), polyethyleneimine dendrimer, polyvinyl alcohol, preoxidized acrylonitrile, polyurethane, epoxy resin, ethylene-vinyl acetate copolymer, polyimide, polycaprolactone, Polypyrrolidone, polydopamine, elastin polypeptide@black scale nanoparticle composite hydrogel, polylactic acid , polyglycolic acid, polylactic acid-glycolic acid copolymer materials and their derivatives, or a combination of two or more.
在一些实施方式中，电极背面修饰的高分子材料层中可以含有抗炎药，所述抗炎药例如包括地塞米松、强的松、保泰松或抗炎性多肽中的一种或多种。高分子材料层中含有抗炎药可使本实用新型柔性电极具有抗炎功能，从而使得柔性电极能长期植入。In some embodiments, the polymer material layer modified on the back of the electrode may contain anti-inflammatory drugs, such as one or more of dexamethasone, prednisone, phenylbutazone or anti-inflammatory polypeptides. kind. The anti-inflammatory drug contained in the polymer material layer can make the flexible electrode of the present invention have an anti-inflammatory function, so that the flexible electrode can be implanted for a long time.
在一些实施方式中，基底层(包括各种具体结构下的基底层)的材料可以包括聚酰亚胺、聚对二甲苯、聚二甲基硅氧烷、医用硅胶、聚(N-异丙基丙烯酰胺)、聚(N-正丙基丙烯酰胺)、聚(N-环丙基丙烯酰胺)、聚(N-异丙基甲基丙烯酰胺)、聚(N-乙基丙烯酰胺)、聚(N-丙烯酰氧基-N-丙基哌嗪)、聚(N-(L)-(1-羟甲基)丙基甲基丙烯酰胺)、聚[N-(2-甲基丙烯酰氧乙基)吡咯烷酮]、聚[N-(3-丙烯酰氧丙基)吡咯烷酮]、聚[N-(3-甲基丙烯酰氧丙基)吡咯烷酮]、聚[N-(2-丙烯酰氧丙基)吡咯烷酮]、聚[N-(1-甲基-2-丙烯酰氧乙基)吡咯烷酮]、聚(2-烷基-2-唑啉)、聚(2-乙基-2-唑啉)、聚(2-异丙基-2-唑啉)、聚(2-正丙基-2-唑啉)、聚甲基丙烯酸二甲氨乙酯、聚(N-乙烯基环己内酰胺)、聚丙烯酰吡咯烷、聚甲基乙烯基醚、聚甲氧基乙基乙烯基醚、聚乙氧基乙基乙烯基醚、聚乙氧基乙氧基乙烯基醚、聚环氧丙烷、聚(低聚(乙二醇)单甲醚甲基丙烯酸酯)、聚有机膦腈、蛋白、弹性蛋白样多肽、琼脂糖、聚乙烯醇、壳聚糖、淀粉、聚丙烯酰胺、聚乙烯吡咯烷酮、透明质酸、透明质酸钠、聚苯乙烯磺酸钠、聚对苯乙烯磺酸、聚甲基丙烯酸羟乙酯、聚乙二醇、聚丁二醇、聚乙二醇甲基丙烯酸酯、聚乙二醇丙烯酸酯、基质胶、明胶、海藻酸、胶原、聚L-赖氨酸、聚L-谷胺酸、羟丙基甲基纤维素、羟乙基纤维素、羧甲基纤维素、羧乙烯聚合物、卡拉胶、玻尿酸、聚乙烯醇、聚甲基丙烯酸甲酯、聚甲基丙烯酸乙酯、聚甲基丙烯酸叔丁基酯、聚丙烯酸甲酯、聚丙烯酸乙酯、聚乙烯基吡啶、聚碳酸酯、聚酰亚胺、醋酸纤维素、尼龙、聚(乙烯基对苯二甲酸酯)、聚磷腈、全氟磺酸、聚乙烯、聚苯乙烯、酚醛树脂、聚丙烯酸、聚L-谷氨酸、聚组氨酸、聚天冬氨酸、聚[(2-二甲基氨基)甲基丙烯酸乙酯]、聚甲基丙烯酸、聚乙基丙烯酸、聚丙基丙烯酸、聚乙烯基苯甲酸、聚衣康酸、聚乙二醇丙烯酸酯磷酸、聚乙二醇甲基丙烯酸酯磷酸、聚乙烯磷酸、聚(4-乙烯基-苯基磷酸)、聚乙烯磺酸、聚(4-苯乙烯磺酸)、聚乙烯苯硼酸、聚甲基丙烯酸二甲氨基乙酯、聚甲基丙烯酸二乙氨基乙酯、聚(N-乙基吡咯烷甲基丙烯酸酯)、聚(2-乙烯基吡啶)、聚(N-丙烯酰基-N-烯基哌嗪)、聚丙烯酰吗啉、聚(4-乙烯基吡啶)、聚乙烯亚胺树状大分子、聚乙烯醇、预氧化丙烯腈、聚氨酯、环氧树脂、乙烯-醋酸乙烯酯共聚物、聚酰亚胺、聚己内酯、聚吡咯烷酮、聚多巴胺、弹性蛋白多肽@黑鳞纳米颗粒复合水凝胶、聚乳酸、聚乙醇酸、聚乳酸-羟基乙酸共聚物材料和它们的衍生物中的一种或多种的复合物、聚氨酯、聚对苯二甲酸乙二醇酯、聚乳酸、聚己内酯、螺吡喃、聚乙二醇、聚乙烯醇、二芳烯、萘并吡喃、偶氮苯、肉桂酰、香豆素、蒽材料和它们的衍生物中的一种或两种以上的组合。In some embodiments, the material of the base layer (including the base layer under various specific structures) may include polyimide, parylene, polydimethylsiloxane, medical silicone, poly(N-isopropyl methacrylamide), poly(N-n-propylacrylamide), poly(N-cyclopropylacrylamide), poly(N-isopropylmethacrylamide), poly(N-ethylacrylamide), Poly(N-acryloxy-N-propylpiperazine), poly(N-(L)-(1-hydroxymethyl)propylmethacrylamide), poly[N-(2-methylpropene Acyloxyethyl)pyrrolidone], poly[N-(3-acryloxypropyl)pyrrolidone], poly[N-(3-methacryloxypropyl)pyrrolidone], poly[N-(2-propylene Acyloxypropyl)pyrrolidone], poly[N-(1-methyl-2-acryloyloxyethyl)pyrrolidone], poly(2-alkyl-2-oxazoline), poly(2-ethyl-2 -oxazoline), poly(2-isopropyl-2-oxazoline), poly(2-n-propyl-2-oxazoline), polydimethylaminoethyl methacrylate, poly(N-vinylcyclo caprolactam), polyacryloylpyrrolidine, polymethyl vinyl ether, polymethoxyethyl vinyl ether, polyethoxyethyl vinyl ether, polyethoxyethoxyvinyl ether, polyepoxy Propane, poly(oligo(ethylene glycol) monomethyl ether methacrylate), polyorganophosphazene, protein, elastin-like polypeptide, agarose, polyvinyl alcohol, chitosan, starch, polyacrylamide, poly Vinylpyrrolidone, Hyaluronic Acid, Sodium Hyaluronate, Sodium Polystyrene Sulfonate, Polyparastyrene Sulfonate, Polyhydroxyethyl Methacrylate, Polyethylene Glycol, Polytetramethylene Glycol, Polyethylene Glycol Methyl Acrylates, Polyethylene Glycol Acrylate, Matrigel, Gelatin, Alginic Acid, Collagen, Poly-L-Lysine, Poly-L-Glutamic Acid, Hydroxypropyl Methyl Cellulose, Hydroxyethyl Cellulose, Carboxymethyl Base cellulose, carboxyvinyl polymer, carrageenan, hyaluronic acid, polyvinyl alcohol, polymethylmethacrylate, polyethylmethacrylate, polytert-butylmethacrylate, polymethylacrylate, polyethylacrylate , polyvinylpyridine, polycarbonate, polyimide, cellulose acetate, nylon, poly(vinyl terephthalate), polyphosphazene, perfluorosulfonic acid, polyethylene, polystyrene, phenolic Resin, polyacrylic acid, poly-L-glutamic acid, polyhistidine, polyaspartic acid, poly[(2-dimethylamino)ethyl methacrylate], polymethacrylic acid, polyethylacrylic acid, Polypropylacrylic acid, polyvinylbenzoic acid, polyitaconic acid, polyethylene glycol acrylate phosphate, polyethylene glycol methacrylate phosphate, polyvinyl phosphate, poly(4-vinyl-phenyl phosphate), poly Vinylsulfonic acid, poly(4-styrenesulfonic acid), polyvinylphenylboronic acid, polydimethylaminoethyl methacrylate, polydiethylaminoethyl methacrylate, poly(N-ethylpyrrolidine methacrylate ester), poly(2-vinylpyridine), poly(N-acryloyl-N-enylpiperazine), polyacryloylmorpholine, poly(4-vinylpyridine), polyethyleneimine dendrimers , polyvinyl alcohol, preoxidized acrylonitrile, polyurethane, epoxy resin, ethylene-vinyl acetate copolymer, Polyimide, polycaprolactone, polypyrrolidone, polydopamine, elastin polypeptide @ black scale nanoparticle composite hydrogel, polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer materials and their derivatives One or more complexes of polyurethane, polyethylene terephthalate, polylactic acid, polycaprolactone, spiropyran, polyethylene glycol, polyvinyl alcohol, diarylene, naphthopyrene One or a combination of two or more of furan, azobenzene, cinnamoyl, coumarin, anthracene materials and their derivatives.
在一些实施方式中，导电层的材料可以包括导电金属材料、导电无机材料和导电高分子材料中的一种或两种以上的组合；优选地，导电金属材料例如包括铂、金、铂铱合金、银、镁、氮化钛、氧化铱、铟锡氧化物、镓铟合金和镓铟锡合金中的一种或两种以上的组合；导电无机材料例如包括石墨烯和碳纳米管中的一种或两种的组合；导电高分子材料例如包括聚吡咯、聚苯硫醚、聚对苯撑、聚苯胺、聚噻吩及它们的衍生物中的一种或两种以上的组合。In some embodiments, the material of the conductive layer may include one or a combination of two or more of conductive metal materials, conductive inorganic materials, and conductive polymer materials; preferably, the conductive metal materials include platinum, gold, and platinum-iridium alloys, for example. , silver, magnesium, titanium nitride, iridium oxide, indium tin oxide, gallium indium alloy and gallium indium tin alloy, or a combination of two or more; conductive inorganic materials include, for example, one of graphene and carbon nanotubes The conductive polymer material includes, for example, one or a combination of two or more of polypyrrole, polyphenylene sulfide, polyparaphenylene, polyaniline, polythiophene and their derivatives.
在一些实施方式中，功能化植入式柔性电极的总厚度为1μm-5.5mm，优选为1μm-300μm，其中，基底层的厚度为1μm-5mm(优选为3μm-10μm)，导电层的厚度为20nm-200μm(优选为20nm-10μm，功能层的厚度为1μm-200μm。此处给出的基底层厚度、导电层厚度、功能层厚度均为功能化植入式柔性电极包括这些层时的厚度，并不代表所有的功能化植入式柔性电极均同时包括这些层。In some embodiments, the total thickness of the functionalized implantable flexible electrode is 1 μm-5.5 mm, preferably 1 μm-300 μm, wherein the thickness of the base layer is 1 μm-5 mm (preferably 3 μm-10 μm), the thickness of the conductive layer is 20nm-200μm (preferably 20nm-10μm, the thickness of the functional layer is 1μm-200μm. The thickness of the base layer, the thickness of the conductive layer, and the thickness of the functional layer given here are all when the functionalized implantable flexible electrode includes these layers. thickness, does not mean that all functionalized implantable flexible electrodes include these layers at the same time.
在一些实施方式中，在功能化植入式柔性电极中，刺激端的尺寸为0.1mm-2cm(优选为0.05mm-1.5cm)，单个刺激位点(一般为圆形)的直径为20nm-5mm(优选为20nm-500μm)，刺激位点的间距为1μm-1mm(优选为1μm-600μm)，刺激位点的数目为10-1000000(优选为60-1000000，更优选为60-100000)。In some embodiments, in the functionalized implantable flexible electrode, the size of the stimulation end is 0.1mm-2cm (preferably 0.05mm-1.5cm), and the diameter of a single stimulation site (generally circular) is 20nm-5mm (preferably 20nm-500μm), the spacing of stimulation sites is 1μm-1mm (preferably 1μm-600μm), and the number of stimulation sites is 10-1000000 (preferably 60-1000000, more preferably 60-100000).
在一些实施方式中，功能化宽幅植入式微电极阵列的总厚度可以为1μm-200μm，其中，基底层的厚度为1μm-20μm，导电层的厚度为20nm-100μm，且刺激端的尺寸为0.1mm-2cm，单个刺激位点的直径为20nm-5mm，刺激位点的间距为1μm-1mm，刺激位点的数目为60-2000。In some embodiments, the total thickness of the functionalized wide-width implantable microelectrode array can be 1 μm-200 μm, wherein the thickness of the base layer is 1 μm-20 μm, the thickness of the conductive layer is 20 nm-100 μm, and the size of the stimulating end is 0.1 mm-2cm, the diameter of a single stimulation site is 20nm-5mm, the distance between stimulation sites is 1μm-1mm, and the number of stimulation sites is 60-2000.
本实用新型的功能植入式柔性电极可以是通过微纳加工、3D打印、印刷、旋涂或喷涂方式制备得到的，可以根据柔性电极的不同结构选择合适的制备方法。The functional implantable flexible electrode of the utility model can be prepared by micro-nano processing, 3D printing, printing, spin coating or spray coating, and an appropriate preparation method can be selected according to different structures of the flexible electrode.
再一方面，本实用新型提供上述的功能化宽幅植入式微电极阵列在制备植入式人造视网膜、植入式人工耳蜗、植入式心植入式脏起搏器、植入式深脑刺激器中的应用。In yet another aspect, the utility model provides the above-mentioned functional wide-width implantable microelectrode array in the preparation of implantable artificial retina, implantable cochlear, implantable cardiac pacemaker, implantable deep brain application of the stimulator.
再一方面，本实用新型提供一种神经假体，其包括上述的功能化宽幅植入式微电极阵列；所述神经假体例如包括植入式人造视网膜、植入式人工耳蜗、植入式心脏起博器或植入式深脑刺激器。In yet another aspect, the utility model provides a neural prosthesis, which includes the above-mentioned functionalized wide-width implantable microelectrode array; A pacemaker or an implanted deep brain stimulator.
相对于现有技术，本实用新型的有益效果为：Compared with the prior art, the beneficial effects of the utility model are:
本实用新型通过光、电、磁、声、热、力触发形成电流或电压的功能层使得本实用新型柔性电极无需复杂的线路连接和器件封装，即可实现神经刺激器件的功能，不仅极大降低了手术风险以及长期植入的安全性风险，更是拓展了神经刺激器件的应用领域。此外，本实用新型还可通过在电极表面进行电化学修饰和生物材料修饰，不仅能够降低电极表面阻抗提升刺激效率，同时能够确保植入器件植入后的生物相容性，防止长期植入的免疫反应。另外，本实用新型还可通过电极背面的高分子材料修饰，使柔性电极具备形状适应性改变功能，这既可以实现微创方式植入，还可以确保电极植入后能有效匹配生物体组织，提高刺激有效性；再者还可以实现电极宽幅设计，增加刺激区域面积，拓展神经刺激功能，例如解决人造视网膜管状视野技术难题。The utility model is triggered by light, electricity, magnetism, sound, heat, and force to form a functional layer of current or voltage, so that the flexible electrode of the utility model can realize the function of the nerve stimulation device without complicated line connection and device packaging, which not only greatly It reduces the risk of surgery and the safety risk of long-term implantation, and expands the application field of nerve stimulation devices. In addition, the utility model can also carry out electrochemical modification and biomaterial modification on the electrode surface, which can not only reduce the electrode surface impedance and improve the stimulation efficiency, but also ensure the biocompatibility of the implanted device after implantation, and prevent long-term implantation. immune response. In addition, the utility model can also modify the polymer material on the back of the electrode to make the flexible electrode have the function of changing the shape adaptively, which can not only realize minimally invasive implantation, but also ensure that the electrode can effectively match the biological tissue after implantation. Improve the effectiveness of stimulation; In addition, it can also realize the wide design of the electrode, increase the area of the stimulation area, and expand the nerve stimulation function, such as solving the technical problem of artificial retinal tubular vision.
总之，本实用新型提供的技术方案，既可以解决现有神经假体长期植入有效性、稳定性与可靠性问题，同时实现神经假体微创植入、适应性匹配组织、大面积刺激等多种功能。In short, the technical solution provided by the utility model can not only solve the problems of long-term implantation effectiveness, stability and reliability of existing neural prosthesis, but also realize minimally invasive implantation of neural prosthesis, adaptive matching tissue, large-area stimulation, etc. A variety of functions.
附图说明Description of drawings
图1为实施例1的电极的刺激位点阵列示意图。FIG. 1 is a schematic diagram of the stimulation site array of the electrodes of Example 1. FIG.
图2为实施例1的功能化宽幅电极的表面修饰效果图。FIG. 2 is a surface modification effect diagram of the functionalized wide-width electrode of Example 1. FIG.
图3为实施例1的功能化宽幅电极卷曲状态(左)以及植入眼球后自展开效果图(右)。Fig. 3 is the crimped state (left) of the functionalized wide-width electrode of Example 1 and the effect diagram of self-expansion after being implanted into the eyeball (right).
图4为窄电极(左)与实施例1的功能化宽幅电极(右)植入后视野拓展效果图。Fig. 4 is a visual field expansion effect diagram after the narrow electrode (left) and the functionalized wide electrode (right) of Example 1 are implanted.
图5为实施例2的功能化电极的表面刺激位点阵列图。FIG. 5 is a diagram of the surface stimulation site array of the functionalized electrode of Example 2. FIG.
图6为实施例3的功能化电极的光致可控形变图。FIG. 6 is a photo-controllable deformation diagram of the functionalized electrode of Example 3. FIG.
图7为实施例3的功能化电极自适应贴合光照点亮LED效果图。Fig. 7 is an effect diagram of the functionalized electrodes of the embodiment 3 adaptively adhering to the light to light up the LED.
具体实施方式Detailed ways
为了对本实用新型的技术特征、目的和有益效果有更加清楚的理解，现结合具体实施例对本实用新型的技术方案进行以下详细说明，应理解这些实例仅用于说明本实用新型而不用于限制本实用新型的范围。实施例中，各原始试剂材料均可商购获得，未注明具体条件的实验方法为所属领域熟知的常规方法和常规条件，或按照仪器制造商所建议的条件。In order to have a clearer understanding of the technical features, purpose and beneficial effects of the present utility model, the technical solutions of the present utility model are now described in detail in conjunction with specific embodiments. It should be understood that these examples are only used to illustrate the utility model and are not intended to limit the present invention Scope of utility model. In the examples, each original reagent material can be obtained commercially, and the experimental methods without specific conditions are conventional methods and conventional conditions well known in the art, or according to the conditions suggested by the instrument manufacturer.
实施例1Example 1
本实施例提供了一种功能化植入式柔性电极，其是一种功能化宽幅电极，该电极包括刺激端、引线部分及功能端，其总长度为6cm，刺激端与功能端通过引线部分连接。其中，刺激端为长方形，长为1.2cm、宽为0.6cm，刺激区域面积为1.2cm×0.6cm，在刺激端内的单个刺激位点直径为300μm，高度为80μm，刺激位点间距为412.5μm，刺激通道数为126；引线部分为长方形，长为4cm，宽为0.4cm，引线间距为10μm；功能端为长方形，长为1.2cm，宽为0.6cm。该电极的刺激端的刺激位点阵列如图1所示。This embodiment provides a functionalized implantable flexible electrode, which is a functionalized wide-width electrode. The electrode includes a stimulating end, a lead part and a functional end, and its total length is 6 cm. The stimulating end and the functional end are passed through the lead wire Partial connection. Among them, the stimulation end is rectangular, with a length of 1.2 cm and a width of 0.6 cm. The area of the stimulation area is 1.2 cm × 0.6 cm. The diameter of a single stimulation site in the stimulation end is 300 μm, the height is 80 μm, and the distance between stimulation sites is 412.5 μm, the number of stimulation channels is 126; the lead part is rectangular, 4cm long, 0.4cm wide, and the lead spacing is 10μm; the functional end is rectangular, 1.2cm long, 0.6cm wide. The stimulation site array of the stimulation end of the electrode is shown in FIG. 1 .
该植入式柔性电极的刺激端包括一层基底层、一层导电层，并且，刺激端的刺激位点上修饰有电镀层、生物材料修饰层，电极的背面接枝有一层聚对苯乙烯磺酸水凝胶层。基底层的材料为聚酰亚胺，其厚度为5μm；导电层的材料为Au，其厚度为50nm；电镀层的材料为铂，其形貌为铂微柱状纳米层，其厚度为0.8μm；生物材料修饰层的材料为聚噻吩，其厚度为0.5μm；电极背面修饰层为聚对苯乙烯磺酸水凝胶层，其厚度为100μm。The stimulating end of the implantable flexible electrode includes a base layer and a conductive layer, and the stimulating site of the stimulating end is decorated with an electroplating layer and a biomaterial modification layer, and a layer of polystyrene sulfonate is grafted on the back of the electrode. acid hydrogel layer. The material of the base layer is polyimide, and its thickness is 5 μm; the material of the conductive layer is Au, and its thickness is 50 nm; the material of the electroplating layer is platinum, and its appearance is a platinum microcolumnar nano-layer, and its thickness is 0.8 μm; The biomaterial modification layer is made of polythiophene with a thickness of 0.5 μm; the modification layer on the back of the electrode is a polyparastyrene sulfonic acid hydrogel layer with a thickness of 100 μm.
该植入式柔性电极的功能端具有一层可通过光触发形成电流的功能层。该功能层的材料为聚三氟乙烯，其厚度为200μm。The functional end of the implantable flexible electrode has a functional layer that can be triggered by light to form an electric current. The material of the functional layer is polytrifluoroethylene, and its thickness is 200 μm.
本实施例的功能化植入式柔性电极是通过以下步骤制备的：The functionalized implantable flexible electrode of this embodiment is prepared through the following steps:
1、宽幅电极的微纳加工制备1. Micro-nano fabrication of wide-width electrodes
以硅为基底，在其上面旋涂聚酰亚胺并固化，随后在其表面采用负胶剥离的方法设计出Au图案化导电层，并进行光刻，随后在导电层上旋涂上一层聚酰亚胺作为绝缘层，并掩模刻蚀暴露出电极和焊盘窗口，并释放出电极。Using silicon as the substrate, polyimide is spin-coated on it and cured, and then the Au patterned conductive layer is designed on the surface by negative adhesive stripping method, and photolithography is performed, and then a layer is spin-coated on the conductive layer Polyimide acts as an insulating layer, and mask etching exposes the electrodes and pad windows, and releases the electrodes.
将偶氮苯聚合物掺杂的聚三氟乙烯通过化学接枝键合的方式于聚酰亚胺(基底层)上形成功能层，以作为功能端，该功能层通过光照就可以产生电流。Polytrifluoroethylene doped with azobenzene polymer is chemically grafted and bonded to form a functional layer on the polyimide (base layer) as a functional terminal, and the functional layer can generate electric current through light irradiation.
2、电极表面修饰2. Electrode surface modification
(a)电化学修饰：在室温环境下，在容器中加入500mL水、2.0mmol的氯铂酸钾和0.08mmol的柠檬酸，并进行超声分散。将上述电极置于前面溶液中，室温下静置48h。随后，将电极浸入超纯水中2h除去未反应的化学物质和粘附性差的铂纳米材料，在电极刺激位点表面得到铂纳米颗粒状纳米层，即电镀层。电化学修饰后的电极阻抗为4.65kΩ·cm2的低阻抗，其阴极电荷存储能力高达25.4mC·cm-2，表面修饰效果如图2所示。(a) Electrochemical modification: At room temperature, 500 mL of water, 2.0 mmol of potassium chloroplatinate and 0.08 mmol of citric acid were added to a container, and ultrasonic dispersion was performed. Place the above electrode in the previous solution and let it stand at room temperature for 48h. Subsequently, the electrode was immersed in ultrapure water for 2 h to remove unreacted chemical substances and platinum nanomaterials with poor adhesion, and a platinum nanoparticle-like nanolayer, that is, an electroplating layer, was obtained on the surface of the electrode stimulation site. The electrode impedance after electrochemical modification is as low as 4.65kΩ·cm2 , and its cathode charge storage capacity is as high as 25.4mC·cm-2 . The surface modification effect is shown in Figure 2.
(b)生物材料修饰：将上述修饰好的电极置于含有0.3M的3,4-乙烯二氧噻吩、0.5M巯基功能化的乙烯基单体的混合液中，在0.5mA·cm-1的电流密度下电镀30min，随后将电极置于超纯水中24h除去未反应化学物质，在电极刺激位点表面得到生物材料修饰层。生物相容性测试结果表明，生物毒性为0级，表明生物相容性效果非常好。(b) Modification of biomaterials: place the modified electrode above in a mixture containing 0.3M 3,4- ethylenedioxythiophene and 0.5M mercapto-functionalized vinyl monomer, and Electroplating was carried out at a current density of 30 min, and then the electrode was placed in ultrapure water for 24 h to remove unreacted chemical substances, and a biomaterial modification layer was obtained on the surface of the electrode stimulation site. The biocompatibility test results show that the biotoxicity is 0 grade, indicating that the biocompatibility effect is very good.
(c)电极背面修饰：将电极背面通过乙烯基硅烷处理聚酰亚胺背面，通过苯乙烯磺酸钠、N-异丙基丙烯酰胺与乙烯基硅烷，以过氧化苯甲酰为引发剂，在90℃热引发聚合下进行化学接枝，在电极背面上接枝共聚一层聚对苯乙烯磺酸水凝胶层。该功能化宽幅电极可以卷曲固定，待植入眼球内后自展开贴合视网膜层，如图3所示，其中，左图为卷曲状态，右图为植入眼球之后自展开的状态。由图3可以看出，该功能电极在植入之前为卷曲状态，尺寸较小，可以很方便地植入眼球之中，植入眼球之后，功能电极在聚对苯乙烯磺酸水凝胶层的带动下自动展开。(c) Modification on the back of the electrode: the back of the electrode is treated with vinyl silane on the back of polyimide, sodium styrene sulfonate, N-isopropylacrylamide and vinyl silane, and benzoyl peroxide as the initiator, The chemical grafting is carried out under thermally initiated polymerization at 90°C, and a poly(p-styrenesulfonic acid) hydrogel layer is grafted and copolymerized on the back of the electrode. The functionalized wide-width electrode can be curled and fixed, and after being implanted in the eyeball, it will self-unfold and fit the retinal layer, as shown in Figure 3, in which the left picture is the curled state, and the right picture is the self-unfolding state after implanting the eyeball. It can be seen from Figure 3 that the functional electrode is in a curled state before implantation, and its size is small, so it can be easily implanted into the eyeball. Driven by the automatic expansion.
3、将电极的刺激端通过引线连接到电极的功能端。由于功能层的存在，使得该电极通过光照即可产生电压进而刺激视神经产生光感信号。由于该电极为宽幅电，极刺激区域比较大，因而可以实现更广阔的视野，较之窄电极获得的管状视野而言，可以极大优化失明患者的视觉恢复效果，如图4所示。3. Connect the stimulating end of the electrode to the functional end of the electrode through the lead wire. Due to the existence of the functional layer, the electrode can generate voltage through light irradiation and stimulate the optic nerve to generate light-sensing signals. Because the electrode is a wide-width electrode, the pole stimulation area is relatively large, so a wider field of view can be achieved. Compared with the tubular field of view obtained by a narrow electrode, it can greatly optimize the visual recovery effect of blind patients, as shown in Figure 4.
实施例2Example 2
本实施例提供了一种功能化植入式柔性电极，该电极具有刺激端及刺激端的引线部分，电极长度为6cm。其中，刺激端(刺激区域)为长方形，面积为1.2cm×0.9cm，在刺激端内的单个刺激位点直径为150μm，刺激位点间距为260μm，刺激通道数为1000，该刺激端的局部结构如图5所示。引线部分面积为1.2cm×0.2cm，引线间距为10μm，单条引线宽为5μm。This embodiment provides a functionalized implantable flexible electrode, the electrode has a stimulating end and a lead part of the stimulating end, and the length of the electrode is 6 cm. Among them, the stimulation end (stimulation area) is a rectangle with an area of 1.2cm×0.9cm, the diameter of a single stimulation site in the stimulation end is 150 μm, the distance between stimulation sites is 260 μm, and the number of stimulation channels is 1000. The local structure of the stimulation end As shown in Figure 5. The area of the lead part is 1.2cm×0.2cm, the distance between the leads is 10μm, and the width of a single lead is 5μm.
该电极的刺激端由一层基底层(复合有可通过光照形成电流的功能材料)、一层导电层组成，并且，刺激端的刺激位点上修饰有电镀层、生物材料修饰层，电极的背面接枝有一层聚己内酯共聚物层。其中，基底层的材料为聚酰亚胺，其厚度为6μm；导电层的材料为Au，其厚度为50nm；可通过光照形成电流的功能材料为钙钛矿光电材料，其厚度为200μm，钙钛矿材料复合在作为基底层的聚酰亚胺之中，其覆盖位置为刺激端的引线部分，功能层连接到刺激位点兼具引线作用；电镀层的材料为铂，其形貌为柱状纳米层，其厚度为350nm；生物材料修饰层的材料为弹性蛋白多肽，其厚度为500nm；电极背面修饰层的材料为聚己内酯共聚物，其厚度为100μm。The stimulating end of the electrode is composed of a base layer (compounded with functional materials that can form current through light) and a conductive layer, and the stimulating site of the stimulating end is decorated with an electroplating layer and a biological material modification layer. The graft has a polycaprolactone copolymer layer. Among them, the material of the base layer is polyimide, and its thickness is 6 μm; the material of the conductive layer is Au, and its thickness is 50 nm; The titanium ore material is compounded in the polyimide as the base layer, and its covering position is the lead part of the stimulation end, and the functional layer connects to the stimulation site and also acts as a lead wire; the material of the electroplating layer is platinum, and its shape is columnar nanometer layer, the thickness of which is 350nm; the material of the biomaterial modification layer is elastin polypeptide, and the thickness is 500nm; the material of the modification layer on the back of the electrode is polycaprolactone copolymer, and the thickness is 100 μm.
该功能电极的光电材料(功能层)产生的电流直接传递到相应刺激位点进而刺激视神经。The current generated by the photoelectric material (functional layer) of the functional electrode is directly transmitted to the corresponding stimulation site to stimulate the optic nerve.
本实施例的功能化植入式柔性电极是通过以下步骤制备的：The functionalized implantable flexible electrode of this embodiment is prepared through the following steps:
1、微纳加工制备电极1. Preparation of electrodes by micro-nano processing
以硅为基底，在其上面旋涂钙钛矿光电材料与聚酰亚胺的复合物作为基底层并固化，随后在其表面采用负胶剥离的方法设计出Au图案化导电层，并进行光刻，随后在导电层上旋涂上一层聚酰亚胺，并掩模刻蚀暴露出电极和焊盘窗口，并释放出电极。Using silicon as the substrate, the composite of perovskite photoelectric material and polyimide was spin-coated on it as the substrate layer and cured, and then the Au patterned conductive layer was designed on the surface by negative adhesive stripping method, and photoelectric Then, a layer of polyimide is spin-coated on the conductive layer, and the mask is etched to expose the electrode and the pad window, and release the electrode.
2、电极表面修饰2. Electrode surface modification
(a)电化学修饰：在室温环境下，在容器中加入500mL水、2.0mmol的氯铂酸和8mmol的柠檬酸，并进行超声分散，得到修饰溶液。将上述电极置于修饰溶液中，以Ag/AgCl为参比电极，通过恒电位方式进行沉积。随后，将电极浸入超纯水中2h除去未反应的化学物质和粘附性差的铂纳米材料，得到柱状纳米层，即电镀层。电化学修饰后的电极阻抗为4.35kΩ·cm2的低阻抗，其阴极电荷存储能力高达26.4mC·cm-2。(a) Electrochemical modification: At room temperature, 500 mL of water, 2.0 mmol of chloroplatinic acid and 8 mmol of citric acid were added to a container, and ultrasonically dispersed to obtain a modification solution. The above electrode is placed in the modification solution, and Ag/AgCl is used as a reference electrode, and the deposition is carried out by a constant potential method. Subsequently, the electrode was immersed in ultrapure water for 2 h to remove unreacted chemicals and poorly adhered platinum nanomaterials to obtain a columnar nanolayer, namely the electroplating layer. The electrode impedance after electrochemical modification is as low as 4.35kΩ·cm2 , and its cathode charge storage capacity is as high as 26.4mC·cm-2 .
(b)生物材料修饰：将上述修饰好的电极通过层层沉积(LBL)的方式沉积生物材料层，具体如下：将电极通过LBL沉积设备程序化地浸入浓度为20wt％的弹性蛋白多肽溶液中，然后提拉起来，并重复该工作100次以组织100层弹性蛋白多肽，即可修饰上弹性蛋白多肽层，得到生物材料修饰层。生物相容性测试结果表明，生物毒性为0级，表明生物相容性效果非常好。(b) Biological material modification: deposit the biomaterial layer on the above-mentioned modified electrode by layer-by-layer deposition (LBL), specifically as follows: programmatically immerse the electrode in an elastin polypeptide solution with a concentration of 20 wt% through the LBL deposition equipment , and then lift it up, and repeat the work 100 times to organize 100 layers of elastin polypeptide, and then the upper elastin polypeptide layer can be modified to obtain a biomaterial modification layer. The biocompatibility test results show that the biotoxicity is 0 grade, indicating that the biocompatibility effect is very good.
(c)电极背面修饰：通过乙烯基硅烷处理聚酰亚胺基底层的背面，通过将背面涂覆有己内酯单体预聚液的电极置于伽马射线源下辐照30min即可实现化学接枝，在电极背面上接枝共聚一层聚己内酯共聚物层。(c) Modification of the back of the electrode: Treat the back of the polyimide base layer with vinyl silane, and irradiate the electrode with the caprolactone monomer pre-polymerization solution on the back for 30 minutes to achieve chemical modification. Grafting, a polycaprolactone copolymer layer is grafted and copolymerized on the back of the electrode.
实施例3Example 3
本实施例提供了功能化植入式柔性电极，该电极如图6所示。该电极包括刺激端、引线部分及功能端，其总长度为6cm，宽度为0.8cm。其中，刺激端的刺激区域面积为0.8cm×1.5cm，在刺激端内的单个刺激位点直径为500μm，刺激位点间距为750μm，刺激通道数为10。引线部分为长方形，其长度为3.0cm，宽度为0.8cm，引线间距为0.5mm。功能端的面积为0.8cm×1.5cm。This embodiment provides a functionalized implantable flexible electrode, as shown in FIG. 6 . The electrode includes a stimulating end, a lead part and a functional end, the total length of which is 6 cm, and the width is 0.8 cm. Among them, the stimulation area of the stimulation end is 0.8cm×1.5cm, the diameter of a single stimulation site in the stimulation end is 500 μm, the distance between stimulation sites is 750 μm, and the number of stimulation channels is 10. The lead part is rectangular, its length is 3.0 cm, its width is 0.8 cm, and the lead wire spacing is 0.5 mm. The area of the functional end is 0.8cm×1.5cm.
该电极的刺激端包括一层基底层、一层导电层，基底层的材料为聚二甲基硅氧烷，其厚度为10μm；导电层的材料为镓铟合金，其厚度为1μm；刺激端的刺激位点上修饰有生物材料修饰层，其材料为聚吡咯，其厚度为0.6μm。The stimulating end of the electrode includes a base layer and a conductive layer. The material of the base layer is polydimethylsiloxane, and its thickness is 10 μm; the material of the conductive layer is gallium indium alloy, and its thickness is 1 μm; The stimulation site is decorated with a biological material modification layer, the material of which is polypyrrole, and the thickness is 0.6 μm.
功能端包括一层基底层和一层功能层，基底层的材料为聚二甲基硅氧烷，其厚度为10μm；功能层的材料为压电材料GaFeO3，其厚度为200μm；The functional end includes a base layer and a functional layer. The material of the base layer is polydimethylsiloxane with a thickness of 10 μm; the material of the functional layer is piezoelectric material GaFeO3 with a thickness of 200 μm;
刺激端和功能端通过引线部分连接在一起；The stimulation end and the function end are connected together through the lead part;
该电极的背面设有电极背面修饰层，其材料为聚丙烯酸水凝胶，其厚度为100μm。The back side of the electrode is provided with an electrode back modification layer, which is made of polyacrylic acid hydrogel with a thickness of 100 μm.
图6左边的图为功能化电极的示意图，显示了电极的结构。通过图6中的左右两个图可以看出该电极的可控形变效果。该功能化植入式柔性电极的功能效果如图7所示，该电极连接有LED灯，采用光照测试该电极的功能效果。在进行光照之前LED不亮，待光照后即点亮LED灯，表明光照后电极在背面修饰层的聚丙烯酸水凝胶的带动下发生形变产生压力，进而由功能层的压电材料产生电流而点亮LED灯。The left panel of Figure 6 is a schematic diagram of a functionalized electrode, showing the structure of the electrode. The controllable deformation effect of the electrode can be seen from the left and right diagrams in FIG. 6 . The functional effect of the functionalized implantable flexible electrode is shown in Figure 7. The electrode is connected to an LED light, and the functional effect of the electrode is tested by light. The LED does not light up before the light is applied, and the LED light is turned on after the light is turned on, indicating that after the light is illuminated, the electrode is deformed under the drive of the polyacrylic acid hydrogel on the back modification layer to generate pressure, and then the piezoelectric material of the functional layer generates a current to Turn on the LED lights.
本实施例的功能化植入式柔性电极是通过以下步骤制备的：The functionalized implantable flexible electrode of this embodiment is prepared through the following steps:
1、3D打印制备电极：以聚二甲基硅氧烷为基底，通过3D打印机将镓铟液态金属打印到基底上固化形成导电层，再用一层Parylene C封装金属线路，暴露出刺激位点，进而获得柔性电极的刺激端。1. Preparation of electrodes by 3D printing: Using polydimethylsiloxane as the substrate, the gallium indium liquid metal is printed on the substrate by a 3D printer and solidified to form a conductive layer, and then a layer of Parylene C is used to encapsulate the metal circuit to expose the stimulation site , and then obtain the stimulating end of the flexible electrode.
以聚二甲基硅氧烷为基底，通过印刷的方式将压电材料GaFeO3形成于基底层表面作为功能层，制备得到功能端。Using polydimethylsiloxane as the base, the piezoelectric material GaFeO3 is formed on the surface of the base layer as a functional layer by printing, and the functional end is prepared.
通过引线部分将刺激端和功能端连接在一起，得到柔性电极。The stimulating end and the functional end are connected together through the lead part to obtain a flexible electrode.
2、电极表面修饰2. Electrode surface modification
(a)生物材料修饰：将上述电极置于含有0.6M的吡咯混合液中，在电流密度为0.8mA·cm-1下电镀30min，随后将电极置于超纯水中24h除去未反应化学物质，得到生物材料修饰层。生物相容性测试结果表明，生物毒性为0级，表明生物相容性效果非常好。(a) Modification of biomaterials: Place the above electrode in a 0.6M pyrrole mixture, electroplate at a current density of 0.8mA cm-1 for 30min, then place the electrode in ultrapure water for 24h to remove unreacted chemical substances , to obtain a biological material modification layer. The biocompatibility test results show that the biotoxicity is 0 grade, indicating that the biocompatibility effect is very good.
(b)电极背面修饰：将电极背面通过乙烯基硅烷处理聚酰亚胺背面，通过以过硫酸铵为引发剂，并加入促进剂在室温下使螺吡喃功能化的丙烯酸单体聚合实现化学接枝，在电极背面上接枝共聚一层螺吡喃功能化的聚丙烯酸水凝胶层。(b) Modification of the back of the electrode: the back of the electrode is treated with vinyl silane on the back of the polyimide, and ammonium persulfate is used as the initiator, and an accelerator is added to polymerize the spiropyran functionalized acrylic monomer at room temperature. Grafting, grafting and copolymerizing a spiropyran functionalized polyacrylic acid hydrogel layer on the back of the electrode.
实施例4Example 4
本实施例提供了一种功能化植入式柔性电极，该电极包括两层基底层、一层导电层、一层LED功能层，其中，一层导电层位于两层基底层中间；基底层的材料为Parylene C，其厚度为10微米，导电层的材料为钛和金，其厚度为80nm；功能层为圆形LED层，其直径为80微米，每个LED灯作为一个刺激位点，其通过外界电源供电进行刺激。该电极的背面接枝有海藻酸钠/壳聚糖复合水凝胶层。This embodiment provides a functionalized implantable flexible electrode, which includes two base layers, a conductive layer, and a LED functional layer, wherein, a conductive layer is located between the two base layers; the base layer The material is Parylene C with a thickness of 10 microns, the material of the conductive layer is titanium and gold, and its thickness is 80 nm; the functional layer is a circular LED layer with a diameter of 80 microns, each LED light serves as a stimulation site, and its Stimulation is provided by an external power supply. The back side of the electrode is grafted with a sodium alginate/chitosan composite hydrogel layer.
本实施例提供的电极是通过以下步骤制备的：The electrode provided in this embodiment is prepared through the following steps:
1、电极的制备1. Electrode preparation
(1.1)在硅片上溅射或热蒸发沉积一层450微米厚的铝作为牺牲层。(1.1) Sputter or thermally evaporate a layer of aluminum with a thickness of 450 microns on the silicon wafer as a sacrificial layer.
(1.2)旋涂一层Parylene C，经过前烘、曝光、显影和固化，制作得到图形化的底层基底层，其厚度为12微米；在光刺激电极底层基底层上面开有三个长方形孔，三个长方形孔的尺寸均为210微米×260微米、中心距为500微米；在光刺激电极底层基底层上面开有两个圆形孔，两个圆形孔的直径均为300微米、中心距为1.5毫米；在光刺激电极底层基底层上面开有四个方形孔，四个方形孔的尺寸为300微米×300微米、中心距为1.5毫米；以上的孔为分别开设。(1.2) Spin-coat one deck of Parylene C, through pre-baking, exposure, development and curing, make the bottom base layer of patterning, its thickness is 12 microns; Have three rectangular holes above the bottom base layer of the photo-stimulation electrode, three The size of each rectangular hole is 210 microns × 260 microns, and the center distance is 500 microns; there are two circular holes on the base layer of the bottom layer of the photostimulation electrode, and the diameter of the two circular holes is 300 microns, and the center distance is 500 microns. 1.5 mm; there are four square holes on the base layer of the bottom layer of the photo-stimulation electrode, the size of the four square holes is 300 microns × 300 microns, and the center distance is 1.5 mm; the above holes are opened separately.
(1.3)溅射一层钛和一层金，厚度分别为28纳米和290纳米，旋涂4微米厚正性光刻胶AZ4620，经过前烘、光刻、显影和后烘，采用湿法刻蚀得到图形化的光刺激电极中间金属层；光刺激电极中间金属层(即钛和金形成的导电层)的一端有三组圆形焊盘，每组包括两个圆，两个圆的直径均为180微米；光刺激电极中间金属层的另一端有四路长方形焊盘，其中一路作为公共电路用于连接所有微型LED裸芯片的阴极金焊盘。(1.3) Sputter a layer of titanium and a layer of gold with a thickness of 28 nanometers and 290 nanometers respectively, spin-coat a 4-micron-thick positive photoresist AZ4620, after pre-baking, photolithography, development and post-baking, use wet etching The patterned photo-stimulation electrode middle metal layer is obtained by etching; one end of the photo-stimulation electrode middle metal layer (i.e. the conductive layer formed by titanium and gold) has three groups of circular pads, each group includes two circles, and the diameters of the two circles are equal. It is 180 microns; the other end of the metal layer in the middle of the photo-stimulation electrode has four rectangular pads, one of which is used as a public circuit to connect the cathode gold pads of all micro-LED bare chips.
(1.4)制作得到图形化的光刺激电极顶层基底层，厚度为9微米，在与光刺激电极底层基底层相同位置处开有一样大小的长方形孔、圆形孔和方孔，同时在光刺激电极中间金属层的圆形焊盘正上方开有三组圆形孔，每组包括两个圆，两个圆的直径均为160微米、间距为730微米。(1.4) The patterned photo-stimulation electrode top basal layer is made, with a thickness of 9 microns. There are rectangular holes, circular holes and square holes of the same size at the same position as the photo-stimulation electrode bottom basal layer. There are three groups of circular holes directly above the circular pad of the metal layer in the middle of the electrode, and each group includes two circles, both of which have a diameter of 160 microns and a pitch of 730 microns.
(1.5)旋涂30微米厚的SU-8胶，经过前烘、曝光、显影和后烘，在光刺激电极顶层基底层上设计放置微型LED裸芯片的长方形凹槽，该长方形凹槽内部尺寸均为240微米×290微米、中心距为500微米。(1.5) Spin-coat SU-8 glue with a thickness of 30 microns. After pre-baking, exposure, development and post-baking, a rectangular groove for placing a micro-LED bare chip is designed on the base layer of the top layer of the light-stimulating electrode. The internal dimensions of the rectangular groove Both are 240 microns × 290 microns, and the center distance is 500 microns.
(1.6)用细针头沾无色透明的耐高温瞬干胶涂抹在长方形凹槽内，如有条件可使用点胶机代替。(1.6) Apply colorless and transparent high-temperature-resistant instant adhesive with a thin needle to the rectangular groove. If possible, use a dispenser instead.
(1.7)用镊子将单个微型LED裸芯片夹起，其阴、阳极金焊盘朝上放置在长方形凹槽内，轻轻按压微型LED裸芯片顶部以确保微型LED裸芯片位置水平，耐高温瞬干胶完全与微型LED裸芯片四周接触且不溢出覆盖顶部，等耐高温瞬干胶固化完成固定；其中：微型LED裸芯片的型号为Cree公司的TR2227、尺寸为220×270×50微米；微型LED裸芯片的阴、阳极金焊盘直径为80微米、间距为135微米。(1.7) Pick up a single micro-LED bare chip with tweezers, place its cathode and anode gold pads facing upwards in the rectangular groove, and gently press the top of the micro-LED bare chip to ensure that the position of the micro-LED bare chip is horizontal, high-temperature instantaneous The dry glue is completely in contact with the surroundings of the micro-LED bare chip and does not overflow to cover the top, and is fixed after the high-temperature resistant instant adhesive is cured; among them: the model of the micro-LED bare chip is Cree's TR2227, and the size is 220×270×50 microns; The cathode and anode gold pads of the bare LED chip have a diameter of 80 microns and a pitch of 135 microns.
(1.8)在金丝球焊机上使用直径25微米的金丝连接微型LED裸芯片的阴、阳极金焊盘和对应的光刺激电极中间金属层一端的圆形焊盘，由于底层聚合物绝缘层为柔性衬底，金丝无法和圆形焊盘牢靠连接，这里仅将金丝的第二键合点轻轻压在圆形焊盘上。(1.8) Use a gold wire with a diameter of 25 microns to connect the negative and anode gold pads of the micro-LED bare chip and the circular pad at one end of the middle metal layer of the corresponding light-stimulating electrode on the gold wire ball welding machine. Due to the insulation of the underlying polymer The first layer is a flexible substrate, and the gold wire cannot be firmly connected to the circular pad. Here, only the second bonding point of the gold wire is lightly pressed on the circular pad.
(1.9)在圆形焊盘上用毛细玻璃管涂抹少量导电银浆，确保金丝和圆形焊盘牢靠连接，尽量保证导电银浆在直径160微米的圆形焊盘范围内。(1.9) Apply a small amount of conductive silver paste on the circular pad with a capillary glass tube to ensure that the gold wire and the circular pad are firmly connected, and try to ensure that the conductive silver paste is within the range of the circular pad with a diameter of 160 microns.
(1.10)在微型LED裸芯片、圆形焊盘和金丝上方用细针头涂抹透明环氧树脂胶以实现封装，保证光刺激电极释放后微型LED裸芯片不会脱落、金线牢固可靠，同时导电银浆不会发生反应。(1.10) Apply transparent epoxy glue on the micro-LED bare chip, round pad and gold wire with a thin needle to realize packaging, so as to ensure that the micro-LED bare chip will not fall off after the light-stimulating electrode is released, and the gold wire is firm and reliable. Conductive silver paste does not react.
(1.11)通过电化学腐蚀或者稀盐酸腐蚀铝牺牲层，完成光刺激电极释放，使用电化学腐蚀法，可以在高浓度NaCl溶液中将光刺激电极放到电解池阳极，电压0.7-1.0V，腐蚀铝牺牲层到光刺激电极自动脱落；使用稀盐酸腐蚀法，可以按照浓盐酸：去离子水＝1：4腐蚀铝牺牲层到光刺激电极自动脱落。(1.11) Corrode the aluminum sacrificial layer by electrochemical corrosion or dilute hydrochloric acid to complete the release of the photo-stimulation electrode. Using the electrochemical corrosion method, the photo-stimulation electrode can be placed on the anode of the electrolytic cell in a high-concentration NaCl solution, and the voltage is 0.7-1.0V. Corrode the aluminum sacrificial layer until the photo-stimulation electrode falls off automatically; using the dilute hydrochloric acid etching method, it can be corroded according to concentrated hydrochloric acid: deionized water = 1:4 to corrode the aluminum sacrificial layer until the photo-stimulation electrode automatically falls off.
2、电极表面修饰2. Electrode surface modification
电极背面修饰：将电极背面(正面是指焊接有LED芯片一侧的基底，背面是没有芯片的那一面)通过plasma处理聚对苯二甲酸乙二醇酯背面，通过LBL方法，在电极背面上接枝一层海藻酸钠/壳聚糖复合水凝胶层。Modification of the back of the electrode: the back of the electrode (the front refers to the substrate on the side where the LED chip is welded, and the back is the side without the chip) is treated with plasma on the back of the polyethylene terephthalate, and the back of the electrode is placed on the back of the electrode by the LBL method. A sodium alginate/chitosan composite hydrogel layer was grafted.
该电极通过功能材料修饰，不仅可以有效解决电极与神经组织间的贴合问题，而且还可以实现光刺激神经组织，拓展多功能神经电极的应用。The electrode is modified with functional materials, which can not only effectively solve the problem of bonding between the electrode and nerve tissue, but also realize light stimulation of nerve tissue and expand the application of multifunctional nerve electrodes.
最后说明的是：以上实施例仅用于说明本实用新型的实施过程和特点，而非限制本实用新型的技术方案，尽管参照上述实施例对本实用新型进行了详细说明，本领域的普通技术人员应当理解：依然可以对本实用新型进行修改或者等同替换，而不脱离本实用新型的精神和范围的任何修改或局部替换，均应涵盖在本实用新型的保护范围当中。Finally, it is explained that the above examples are only used to illustrate the implementation process and characteristics of the present utility model, rather than limiting the technical solution of the present utility model. Although the utility model has been described in detail with reference to the above examples, those of ordinary skill in the art It should be understood that the utility model can still be modified or equivalently replaced, and any modification or partial replacement without departing from the spirit and scope of the utility model should be covered by the protection scope of the utility model.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201821989495.5UCN209519237U (en) | 2018-11-29 | 2018-11-29 | A kind of functionalization implanted flexible electrode |
| Application Number | Priority Date | Filing Date | Title |
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| CN201821989495.5UCN209519237U (en) | 2018-11-29 | 2018-11-29 | A kind of functionalization implanted flexible electrode |
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| CN209519237Utrue CN209519237U (en) | 2019-10-22 |
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| CN201821989495.5UActiveCN209519237U (en) | 2018-11-29 | 2018-11-29 | A kind of functionalization implanted flexible electrode |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109350847A (en)* | 2018-11-29 | 2019-02-19 | 深圳先进技术研究院 | A functionalized implantable flexible electrode and its application |
| CN111013014A (en)* | 2019-12-17 | 2020-04-17 | 中国科学院深圳先进技术研究院 | Nerve tissue stimulation composite material, composite membrane and nerve tissue prosthesis |
| CN113694371A (en)* | 2021-08-25 | 2021-11-26 | 杭州维纳安可医疗科技有限责任公司 | Implanted electrode and electric field treatment equipment |
| WO2022233140A1 (en)* | 2021-05-07 | 2022-11-10 | 中国科学院深圳先进技术研究院 | Implant interface modification material, implant, and preparation method therefor |
| US20230087381A1 (en)* | 2020-03-10 | 2023-03-23 | iCOMMISSARIAT À L'ÉNERGIE ATOMIQUE ET AUX ÉNERGIES ALTERNATIVES | Amyloid fibers based electrodes |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109350847A (en)* | 2018-11-29 | 2019-02-19 | 深圳先进技术研究院 | A functionalized implantable flexible electrode and its application |
| CN111013014A (en)* | 2019-12-17 | 2020-04-17 | 中国科学院深圳先进技术研究院 | Nerve tissue stimulation composite material, composite membrane and nerve tissue prosthesis |
| US20230087381A1 (en)* | 2020-03-10 | 2023-03-23 | iCOMMISSARIAT À L'ÉNERGIE ATOMIQUE ET AUX ÉNERGIES ALTERNATIVES | Amyloid fibers based electrodes |
| WO2022233140A1 (en)* | 2021-05-07 | 2022-11-10 | 中国科学院深圳先进技术研究院 | Implant interface modification material, implant, and preparation method therefor |
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| WO2024227312A1 (en)* | 2023-05-04 | 2024-11-07 | 深圳先进技术研究院 | Bionic vision restoration material and preparation method therefor, restoration membrane and preparation method therefor, and restoration device |
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