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1. 发明申请

WO2011137298A3 IMPROVED BIOCOMPATIBLE BONDING METHOD 审中-公开
公开(公告)号：WO2011137298A3
公开(公告)日：2011-11-03
申请号：PCT/US2011/034471
申请日：2011-04-29
申请人： SECOND SIGHT MEDICAL PRODUCTS,INC. , FARAJI, Boozarjomehr , ZHOU, David, Daomin , GREENBERG, Robert, J. , OK, Jerry , TALBOT, Neil, Hamilton , LITTLE, James, Singleton
发明人： FARAJI, Boozarjomehr , ZHOU, David, Daomin , GREENBERG, Robert, J. , OK, Jerry , TALBOT, Neil, Hamilton , LITTLE, James, Singleton
IPC分类号： A61N1/36 , A61N1/375 , H01L21/60 , H01L21/56 , A61B5/04
摘要： The invention is a device and method for connecting a hermetic package to a flexible circuit such as for an electrode array in an implantable device. Attaching metal pads on a flexible circuit to metal pads on a hermetic device by conductive adhesive is known. A smooth metal, such as platinum, does not bond well to conductive epoxy. The invention provides a roughened surface, such as by etching or by applying high surface area platinum gray, to improve adhesion to platinum or other metal pads.

2. 发明申请

WO2009142888A2 IMMORTAL UNIPOTENT PORCINE PICM- 19H AND PICM- 19B STEM CELL LINES 审中-公开
标题翻译：独立的无线电PICM-19H和PICM-19B干线电缆
公开(公告)号：WO2009142888A2
公开(公告)日：2009-11-26
申请号：PCT/US2009042344
申请日：2009-04-30
申请人： US AGRICULTURE , TALBOT NEIL C , CAPERNA THOMAS J , WILLARD RYAN
发明人： TALBOT NEIL C , CAPERNA THOMAS J , WILLARD RYAN
IPC分类号： A61F2/02 , C12N5/02 , C12N5/074 , C12N11/00 , G01N33/15
CPC分类号： C12N5/0672 , C12N11/00 , C12N11/02 , C12N11/04
摘要： Two cell lines, PICM-19H and PICM-19B, were derived from the bipotent ARS-PICM- 19 pig liver stem cell line and assessed for their potential application in artificial liver devices. The study included assessments of growth rate and cell density in culture, morphological features, and hepatocyte detoxification functions, i.e., inducible CYP450 activity, ammonia clearance, and urea production. The PICM-19H cells contain numerous mitochondria, Golgi apparatus, smooth and rough endoplasmic reticulum, vesicular bodies and occasional lipid vacuoles. PICM-19H cells display inducible CYP450 activity, clear ammonia, and produce urea in a glutamine-free medium. Ultrastructural analysis of the PICM- 19B monolayers show that the roughly cuboidal cells display basal-apical polarization and are joined by tight junction-like complexes. Other ultrastructure features are similar to those of PICM- 19H cells except that they possess numerous cell bodies resembling mucus vacuoles. The PICM-19B cells possess relatively high levels of GGT activity, but retain some inducible CYP450 activity, and some ammonia clearance and urea synthesis ability. These data indicate that both cell lines, either together or alone, may be useful as the cellular substrate for an artificial liver device. In vitro models of the liver are needed to replace animal models for the rapid assessment of drug biotransformation and toxicity. A unipotent porcine stem cell line PICM- 19H differentiates exclusively into hepatocytes and can be induced to express CYP450 enzymes. These cells have many activities associated with xenobiotic phase I - and phase II metabolism lacking in other liver cell lines. The PICM- 19H cell line was also compared to the tumor-derived human HepG2 C3A cell line and to primary cultures of adult porcine hepatocytes. The results demonstrate the potential for the use of PICM- 19H cells in drug biotransformation and toxicity testing and further support their use in artificial liver device technology.
摘要翻译：两条细胞系PICM-19H和PICM-19B衍生自双能ARS-PICM-19猪肝干细胞系，并评估其在人工肝脏装置中的潜在应用。该研究包括培养中的生长速率和细胞密度，形态特征和肝细胞解毒功能的评估，即诱导型CYP450活性，氨清除和尿素生产。 PICM-19H细胞含有许多线粒体，高尔基体，光滑粗糙的内质网，囊泡体和偶尔的脂质空泡。 PICM-19H细胞显示可诱导的CYP450活性，清除氨，并在无谷氨酰胺培养基中产生尿素。 PICM-19B单层膜的超微结构分析表明，粗略的立方体细胞显示出基底顶端极化，并通过紧密连接状复合体连接。其他超微结构特征与PICM-19H细胞相似，除了它们具有许多类似于粘液空泡的细胞体。 PICM-19B细胞具有较高水平的GGT活性，但保留一些可诱导的CYP450活性，以及一些氨清除和尿素合成能力。这些数据表明，两个细胞系一起或单独使用，可用作人造肝器具的细胞底物。肝脏的体外模型需要替代动物模型以快速评估药物生物转化和毒性。单能猪干细胞系PICM-19H分化为肝细胞，可诱导表达CYP450酶。这些细胞具有许多与异种生物相I相关的活性，而在其它肝细胞系中缺乏二期代谢。还将PICM-19H细胞系与肿瘤来源的人HepG2 C3A细胞系和成年猪肝细胞的原代培养物进行比较。结果表明在药物生物转化和毒性测试中使用PICM-19H细胞的潜力，并进一步支持其在人工肝脏装置技术中的应用。

3. 发明申请

WO2007149571A3 FLEXIBLE CIRCUIT ELECTRODE ARRAY WITH AT LEAST ONE TACK OPENING 审中-公开
标题翻译：至少一次开启柔性电路阵列电极阵列
公开(公告)号：WO2007149571A3
公开(公告)日：2008-06-26
申请号：PCT/US2007014618
申请日：2007-06-21
申请人： SECOND SIGHT MEDICAL PROD INC , GREENBERG ROBERT J , TALBOT NEIL HAMILTON , NEYSMITH JORDAN , LITTLE JAMES S , MECH BRIAN V
发明人： GREENBERG ROBERT J , TALBOT NEIL HAMILTON , NEYSMITH JORDAN , LITTLE JAMES S , MECH BRIAN V
IPC分类号： A61N1/05
CPC分类号： A61N1/0543 , A61N1/36046 , H05K1/118 , H05K3/0014 , Y10T29/49002 , Y10T29/49117 , Y10T29/49155 , Y10T29/49156 , Y10T29/49158 , Y10T29/49174 , Y10T29/49176
摘要： The present invention provides a flexible circuit electrode array adapted for neural stimulation, comprising: a polymer base layer; metal traces deposited on said polymer base layer, including electrodes suitable to stimulate neural tissue; a polymer top layer deposited on said polymer base layer and said metal traces at least one tack opening; wherein said polymer base layer, said metal traces and said polymer top layer are thermoformed in a three dimensional shape. The present invention provides further a method of making a flexible circuit electrode array comprising depositing a polymer base layer; depositing metal on said polymer base layer; patterning said metal to form metal traces; depositing a polymer top layer on said polymer base layer and said metal traces; preparing at least one tack opening; and heating said flexible circuit electrode array in a mold to form a three dimensional shape in said flexible circuit electrode array.
摘要翻译：本发明提供了一种适用于神经刺激的柔性电路电极阵列，包括：聚合物基层; 沉积在所述聚合物基层上的金属迹线，包括适于刺激神经组织的电极; 沉积在所述聚合物基层上的聚合物顶层，并且所述金属跟踪至少一个开口; 其中所述聚合物基层，所述金属迹线和所述聚合物顶层以三维形状热成形。本发明进一步提供一种制造柔性电路电极阵列的方法，该方法包括沉积聚合物基层; 在所述聚合物基底层上沉积金属; 图案化所述金属以形成金属迹线; 在所述聚合物基底层和所述金属迹线上沉积聚合物顶层; 准备至少一个平头开口; 以及在模具中加热所述柔性电路电极阵列以在所述柔性电路电极阵列中形成三维形状。

4. 发明申请

WO2008021524A2 PACKAGE FOR AN IMPLANTABLE NEURAL STIMULATION DEVICE 审中-公开
标题翻译：可植入神经刺激装置的包装
公开(公告)号：WO2008021524A2
公开(公告)日：2008-02-21
申请号：PCT/US2007018315
申请日：2007-08-18
申请人： SECOND SIGHT MEDICAL PROD INC , OK JERRY , GREENBERG ROBERT J , TALBOT NEIL HAMILTON , LITTLE JAMES SINGLETON , DAI RONGQING , NEYSMITH JORDAN MATTHEW , MCCLURE KELLY H
发明人： OK JERRY , GREENBERG ROBERT J , TALBOT NEIL HAMILTON , LITTLE JAMES SINGLETON , DAI RONGQING , NEYSMITH JORDAN MATTHEW , MCCLURE KELLY H
IPC分类号： A61N1/00
CPC分类号： A61N1/36046 , A61F15/001 , A61N1/0529 , A61N1/0543 , A61N1/36125 , A61N1/375 , H01L23/055 , H01L23/06 , H01L23/08 , H01L23/10 , H01L24/16 , H01L24/48 , H01L25/18 , H01L2224/16225 , H01L2224/45144 , H01L2224/48091 , H01L2224/48106 , H01L2224/48225 , H01L2924/00014 , H01L2924/00 , H01L2224/0401
摘要： The present invention is an improved hermetic package for implantation in the human body. The implantable device comprises an electrically non-conductive substrate; a plurality of electrically conductive vias through said electrically non-conductive substrate; a flip-chip circuit attached to said electrically non-conductive substrate using conductive bumps and electrically connected to a first subset of said plurality of electrically conductive vias, wherein said flip-chip circuit contains one or more stacks or a folded stack; a wire bonded circuit attached to said electrically non-conductive substrate and electrically connected to a second subset of said electrically conductive vias; and a cover bonded to said electrically non-conductive substrate, said cover, said electrically non-conductive substrate and said electrically conductive vias forming a hermetic package.
摘要翻译：本发明是用于植入人体的改进的密封包装。可植入装置包括非导电基底; 通过所述非导电衬底的多个导电通孔; 使用导电凸块连接到所述非导电衬底并电连接到所述多个导电通孔的第一子集的倒装芯片电路，其中所述倒装芯片电路包含一个或多个堆叠或折叠堆叠; 连接到所述非导电衬底并电连接到所述导电通孔的第二子集的引线键合电路; 以及盖，其结合到所述非导电衬底，所述盖，所述非导电衬底和所述导电通孔形成气密封装。

5. 发明申请

WO2007058975A3 POLYMER LAYER COMPRISING SILICONE AND AT LEAST ONE METAL TRACE AND A PROCESS OF MANUFACTURING THE SAME 审中-公开
标题翻译：包含硅胶和至少一种金属追踪的聚合物层及其制造方法
公开(公告)号：WO2007058975A3
公开(公告)日：2008-01-24
申请号：PCT/US2006043863
申请日：2006-11-10
申请人： SECOND SIGHT MEDICAL PROD INC , DOHENY EYE INST , LAUDE LUCIEN , TALBOT NEIL HAMILTON , GREENBERG ROBERT J
发明人： LAUDE LUCIEN , TALBOT NEIL HAMILTON , GREENBERG ROBERT J
IPC分类号： C23C18/16 , C23C18/20 , G03F7/20
CPC分类号： G03F7/265 , C23C18/1608 , C23C18/1612 , C23C18/1868 , C23C18/31 , H05K1/0283 , H05K1/0289 , H05K1/032 , H05K1/0373 , H05K1/0393 , H05K3/007 , H05K3/107 , H05K3/185 , H05K3/28 , H05K2201/0133 , H05K2201/0162 , H05K2201/0209 , H05K2203/016
摘要： The present invention relates to a process for embedding at least one layer of at least one metal trace in a silicone containing polymer, comprising: a) applying a non adhering on a substrate; b) applying a polymer layer on the non adhering agent; c) irradiation at least one surface area of said polymer with a light beam emitted by an excimer laser; d) immersing said irradiated polymer in at least one autocatalytic bath containing metal ions of at least one metal and metallizing the polymer; e) thermally treating said metallized polymer; f) applying a polymer layer on said thermally treated metallized polymer; and g) thermally treating said metallized polymer.
摘要翻译：本发明涉及一种在含硅氧烷聚合物中嵌入至少一层至少一种金属迹线的方法，包括：a）将不粘附在基底上; b）在非粘合剂上施加聚合物层; c）用由准分子激光器发射的光束照射所述聚合物的至少一个表面积; d）将所述照射的聚合物浸入至少一种含有至少一种金属的金属离子并使聚合物金属化的自催化浴; e）热处理所述金属化聚合物; f）将聚合物层施加在所述热处理的金属化聚合物上; 和g）热处理所述金属化聚合物。

6. 发明申请

WO2007149571A2 FLEXIBLE CIRCUIT ELECTRODE ARRAY WITH AT LEAST ONE TACK OPENING 审中-公开
标题翻译：柔性电路电极阵列至少打开一个
公开(公告)号：WO2007149571A2
公开(公告)日：2007-12-27
申请号：PCT/US2007/014618
申请日：2007-06-21
申请人： SECOND SIGHT MEDICAL PRODUCTS, INC. , GREENBERG, Robert, J. , TALBOT, Neil, Hamilton , NEYSMITH, Jordan , LITTLE, James, S. , MECH, Brian, V.
发明人： GREENBERG, Robert, J. , TALBOT, Neil, Hamilton , NEYSMITH, Jordan , LITTLE, James, S. , MECH, Brian, V.
CPC分类号： A61N1/0543 , A61N1/36046 , H05K1/036 , H05K1/0393 , H05K1/118 , H05K3/0014 , H05K2201/05 , H05K2201/053 , H05K2201/09063 , H05K2201/09409 , Y10T29/49002 , Y10T29/49117 , Y10T29/49155 , Y10T29/49156 , Y10T29/49158 , Y10T29/49174 , Y10T29/49176
摘要： The present invention provides a flexible circuit electrode array adapted for neural stimulation, comprising: a polymer base layer; metal traces deposited on said polymer base layer, including electrodes suitable to stimulate neural tissue; a polymer top layer deposited on said polymer base layer and said metal traces at least one tack opening; wherein said polymer base layer, said metal traces and said polymer top layer are thermoformed in a three dimensional shape. The present invention provides further a method of making a flexible circuit electrode array comprising depositing a polymer base layer; depositing metal on said polymer base layer; patterning said metal to form metal traces; depositing a polymer top layer on said polymer base layer and said metal traces; preparing at least one tack opening; and heating said flexible circuit electrode array in a mold to form a three dimensional shape in said flexible circuit electrode array.
摘要翻译：本发明提供一种适用于神经刺激的柔性电路电极阵列，包括：聚合物基层; 沉积在所述聚合物基层上的金属痕迹，包括适于刺激神经组织的电极; 沉积在所述聚合物基层上的聚合物顶层和所述金属迹线至少一个粘性开口; 其中所述聚合物基层，所述金属迹线和所述聚合物顶层被热成型为三维形状。本发明还提供一种制造柔性电路电极阵列的方法，包括沉积聚合物基层; 在所述聚合物基层上沉积金属; 图案化所述金属以形成金属痕迹; 在所述聚合物基底层和所述金属迹线上沉积聚合物顶层; 准备至少一个开口; 并将所述柔性电路电极阵列加热到模具中，以在所述柔性电路电极阵列中形成三维形状。

7. 发明申请

WO2007149465A3 ELECTRODE WITH INCREASED STABILITY AND METHOD OF MANUFACTURING THE SAME 审中-公开
公开(公告)号：WO2007149465A3
公开(公告)日：2007-12-27
申请号：PCT/US2007/014332
申请日：2007-06-19
申请人： SECOND SIGHT MEDICAL PRODUCTS, INC. , ZHOU, Dao, Min , OK, Jerry , TALBOT, Neil, Hamilton , MECH, Brian, V. , LITTLE, James , GREENBERG, Robert, J.
发明人： ZHOU, Dao, Min , OK, Jerry , TALBOT, Neil, Hamilton , MECH, Brian, V. , LITTLE, James , GREENBERG, Robert, J.
IPC分类号： A61N1/05 , A61N1/36
摘要： The present invention provides an implantable electrode with increased stability having a clustered structure wherein the surface of the electrode is covered with a material comprising openings which are filled with sticks or posts. The present invention provides an implantable electrode with increased stability wherein the surface is of the electrode comprises mesh grids which are filled with sticks which are filed with a conducting or insulating material. The present invention provides a method of manufacturing an electrode with increased stability, comprising: depositing a metal layer on an base layer; applying photoresist layer on the metal layer; patterning the photoresist layer providing openings; electroplating the openings with metal; removing the photoresist layer leaving spaces; and filling the spaces with polymer. The present invention provides a method of manufacturing an electrode with increased stability, comprising: depositing a metal layer on an base layer; applying a polymer layer on the metal layer; applying photoresist layer on the polymer layer; patterning the photoresist layer providing openings; electroplating the openings with metal; and removing the photoresist layer.

8. 发明申请

WO2006116765A2 FLEXIBLE CIRCUIT ELECTRODE ARRAY 审中-公开
标题翻译：柔性电路阵列
公开(公告)号：WO2006116765A2
公开(公告)日：2006-11-02
申请号：PCT/US2006016655
申请日：2006-04-28
申请人： SECOND SIGHT MEDICAL PROD INC , GREENBERG ROBERT JAY , TALBOT NEIL , NEYSMITH JORDAN , LITTLE JAMES S , MECH BRIAN V , HUMAYAN MARK , GUVEN DILEK , RIPLEY ANN MARIE DE MERLIER
发明人： GREENBERG ROBERT JAY , TALBOT NEIL , NEYSMITH JORDAN , LITTLE JAMES S , MECH BRIAN V , HUMAYAN MARK , GUVEN DILEK , RIPLEY ANN MARIE DE MERLIER
IPC分类号： A61N1/05
CPC分类号： H05K3/0011 , A61N1/0541 , A61N1/0543 , A61N1/36036 , A61N1/36046 , Y10T29/49124
摘要： Polymer materials are useful as electrode array bodies for neural stimulation. They are particularly useful for retinal stimulation to create artificial vision, cochlear stimulation to create artificial hearing, or cortical stimulation many purposes. The pressure applied against the retina, or other neural tissue, by an electrode array is critical. Too little pressure causes increased electrical resistance, along with electric field dispersion. Too much pressure may block blood flow. Common flexible circuit fabrication techniques generally require that a flexible circuit electrode array be made flat. Since neural tissue is almost never flat, a flat array will necessarily apply uneven pressure. Further, the edges of a flexible circuit polymer array may be sharp and cut the delicate neural tissue. By applying the right amount of heat to a completed array, a curve can be induced. With a thermoplastic polymer it may be further advantageous to repeatedly heat the flexible circuit in multiple molds, each with a decreasing radius. Further, it is advantageous to add material along the edges. It is further advantageous to provide a fold or twist in the flexible circuit array. Additional material may be added inside and outside the fold to promote a good seal with tissue.
摘要翻译：聚合物材料可用作神经刺激的电极阵列体。它们对视网膜刺激特别有用，用于创建人造视觉，人工耳蜗刺激以创建人造听觉或皮质刺激许多目的。通过电极阵列对视网膜或其他神经组织施加的压力是至关重要的。太小的压力会导致电阻增加以及电场分散。太大的压力可能会阻止血液流动。通常的柔性电路制造技术通常需要使柔性电路电极阵列平坦。由于神经组织几乎从不平坦，平面阵列必然会施加不均匀的压力。此外，柔性电路聚合物阵列的边缘可以是尖锐的并切割精细的神经组织。通过将适量的热应用于完整的阵列，可以引起曲线。对于热塑性聚合物，可以进一步有利的是在多个模具中反复加热柔性电路，每个模具具有减小的半径。此外，沿着边缘添加材料是有利的。在柔性电路阵列中提供折叠或扭曲是更有利的。可以在折叠内部和外部添加附加材料以促进与组织的良好密封。

9. 发明申请

WO2009142888A3 IMMORTAL UNIPOTENT PORCINE PICM- 19H AND PICM- 19B STEM CELL LINES 审中-公开
公开(公告)号：WO2009142888A3
公开(公告)日：2009-11-26
申请号：PCT/US2009/042344
申请日：2009-04-30
申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF AGRICULTURE , TALBOT, Neil, C. , CAPERNA, Thomas, J. , WILLARD, Ryan
发明人： TALBOT, Neil, C. , CAPERNA, Thomas, J. , WILLARD, Ryan
IPC分类号： C12N5/06 , C12N5/02 , C12N11/00 , A61F2/02 , G01N33/15
摘要： Two cell lines, PICM-19H and PICM-19B, were derived from the bipotent ARS-PICM- 19 pig liver stem cell line and assessed for their potential application in artificial liver devices. The study included assessments of growth rate and cell density in culture, morphological features, and hepatocyte detoxification functions, i.e ., inducible CYP450 activity, ammonia clearance, and urea production. The PICM-19H cells contain numerous mitochondria, Golgi apparatus, smooth and rough endoplasmic reticulum, vesicular bodies and occasional lipid vacuoles. PICM-19H cells display inducible CYP450 activity, clear ammonia, and produce urea in a glutamine-free medium. Ultrastructural analysis of the PICM- 19B monolayers show that the roughly cuboidal cells display basal-apical polarization and are joined by tight junction-like complexes. Other ultrastructure features are similar to those of PICM- 19H cells except that they possess numerous cell bodies resembling mucus vacuoles. The PICM-19B cells possess relatively high levels of GGT activity, but retain some inducible CYP450 activity, and some ammonia clearance and urea synthesis ability. These data indicate that both cell lines, either together or alone, may be useful as the cellular substrate for an artificial liver device. In vitro models of the liver are needed to replace animal models for the rapid assessment of drug biotransformation and toxicity. A unipotent porcine stem cell line PICM- 19H differentiates exclusively into hepatocytes and can be induced to express CYP450 enzymes. These cells have many activities associated with xenobiotic phase I - and phase II metabolism lacking in other liver cell lines. The PICM- 19H cell line was also compared to the tumor-derived human HepG2 C3A cell line and to primary cultures of adult porcine hepatocytes. The results demonstrate the potential for the use of PICM- 19H cells in drug biotransformation and toxicity testing and further support their use in artificial liver device technology.

10. 发明申请

WO2009132296A1 SIMPLY SUPPORTED NEURAL STIMULATION ELECTRODE ARRAY FOR APPLYING PRESSURE ON NEURAL TISSUE 审中-公开
标题翻译：简单支持的神经刺激电极阵列在神经组织上施加压力
公开(公告)号：WO2009132296A1
公开(公告)日：2009-10-29
申请号：PCT/US2009/041701
申请日：2009-04-24
申请人： SECOND SIGHT MEDICAL PRODUCTS , GREENBERG, Robert, J. , KHALDI, Mohamed , LITTLE, James, S. , NEYSMITH, Jordan, M. , TALBOT, Neil, Hamilton
发明人： GREENBERG, Robert, J. , KHALDI, Mohamed , LITTLE, James, S. , NEYSMITH, Jordan, M. , TALBOT, Neil, Hamilton
IPC分类号： A61N1/05 , A61N1/36
CPC分类号： A61N1/0543 , A61N1/36046
摘要： The present invention is an electrode array for neural stimulation suitable to be attached to neural tissue such that the attachment point acts as a fulcrum like point and contact with an end of the array body presses the other end of the array body into the neural tissue to be stimulated. This invention is particularly useful in a retinal electrode array for a visual prosthesis. By curving an electrode portion of an array body to approximate but not exceed (never more tightly curved) the curvature of the retina and applying force to the array by external means at the fulcrum like point, approximately even pressure across all electrodes is achieved.
摘要翻译：本发明是一种用于神经刺激的电极阵列，其适用于附着于神经组织，使得附着点作为支点，并且与阵列体的端部接触将阵列体的另一端压入神经组织，被刺激。本发明在用于视觉假体的视网膜电极阵列中特别有用。通过将阵列体的电极部分弯曲成近似但不超过（从不更紧密地弯曲）视网膜的曲率并且通过外部装置在支点点处向阵列施加力，实现了跨所有电极的大致均匀的压力。

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