公开(公告)号：US20060030812A1

公开(公告)日：2006-02-09

申请号：US11133245

申请日：2005-05-20

Applicant: Nevenka Golubovic-Liakopoulos ,  Glenn Fricano ,  Michael Danielson

Inventor： Nevenka Golubovic-Liakopoulos ,  Glenn Fricano ,  Michael Danielson

IPC: A61B17/20

CPC classification number: B81C1/00111 ,  A61B17/205 ,  A61B2017/00526 ,  A61M37/0015 ,  A61M2037/003 ,  A61M2037/0053 ,  B81B2201/055

Abstract: The invention relates to a method of fabricating a microneedle array in a substrate, a drug delivery device comprising one or more microneedles extending upwards from the front surface of the substrate, the microneedles having a generally conical-shaped body defined by a plurality of surfaces sloping upwards from a relatively broad base to a tip, and one or more substances coating the microneedles, the one or more substances being operable to be administered to a patient, wherein the tips of the one or more microneedles are sufficiently sharp to penetrate an outer layer of the skin of the patient, and a method of administering one or more substances to a patient using the device.

公开(公告)号：US06980855B2

公开(公告)日：2005-12-27

申请号：US10767485

申请日：2004-01-29

Applicant: Steve T. Cho

Inventor： Steve T. Cho

IPC: B81B1/00 ,  A61B5/15 ,  A61M5/32 ,  A61M37/00 ,  B81C1/00 ,  A61N1/30

CPC classification number: B81C1/00111 ,  A61B5/14514 ,  A61B5/150022 ,  A61B5/150221 ,  A61B5/150282 ,  A61B5/150748 ,  A61B5/15087 ,  A61B5/150969 ,  A61B5/150984 ,  A61B5/157 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0038 ,  A61M2037/0053 ,  B81B2201/055

Abstract: The present invention provides a microneedle incorporating a base that is broad relative to a height of the microneedle, to minimize breakage. The microneedle further includes a fluid channel and a beveled non-coring tip. Preferably arrays of such microneedles are fabricated utilizing conventional semiconductor derived micro-scale fabrication techniques. A dot pattern mask is formed on an upper surface of a silicon substrate, with each orifice of the dot pattern mask corresponding to a desired location of a microneedle. Orifices are formed that pass completely through the substrate by etching. A nitride pattern mask is formed to mask all areas in which a nitride layer is not desired. A nitride layer is then deposited on the bottom of the silicon substrate, on the walls of the orifice, and on the top of the silicon substrate around the periphery of the orifice. The nitride layer around the periphery of the orifice is offset somewhat, such that one side of the orifice has a larger nitride layer. Anisotropic etching is used to remove a substantial portion of the substrate, creating a plurality of angular, blunt, and generally pyramidal-shaped microneedles. A subsequent removal of the nitride layer, followed by an isotropic etching step, softens and rounds out the blunt angular microneedles, providing generally conical-shaped microneedles. The uneven nitride layer adjacent the orifice ensures that the microneedles will include a beveled tip. Such microneedle arrays are preferably incorporated into handheld diagnostic and drug delivery systems.

Abstract translation: 本发明提供了一种结合了相对于微针的高度宽的基底的微针，以使破损最小化。 微针还包括流体通道和倾斜的非取心尖端。 优选地，使用常规的半导体衍生的微尺度制造技术制造这种微针的阵列。 在硅基板的上表面上形成点阵图案掩模，点图案掩模的每个孔口对应于微针的期望位置。 形成通过蚀刻完全通过基板的孔。 形成氮化物图案掩模以掩盖不需要氮化物层的所有区域。 然后将氮化物层沉积在硅衬底的底部，孔的壁上，以及围绕孔的周边的硅衬底的顶部上。 围绕孔的周边的氮化物层稍微偏移，使得孔的一侧具有较大的氮化物层。 使用各向异性蚀刻去除基本部分的大部分，产生多个角，钝，通常为锥形的微针。 随后去除氮化物层，随后进行各向同性的蚀刻步骤，软化和圆化钝角微针，提供大致锥形的微针。 邻近孔口的不均匀氮化物层确保了微针将包括一个倾斜尖端。 这种微针阵列优选并入手持诊断和药物输送系统中。

公开(公告)号：US20050163931A1

公开(公告)日：2005-07-28

申请号：US10508128

申请日：2002-07-12

Applicant: Ningsheng Xu ,  Shaozhi Deng ,  Juncong She ,  Jun Chen

Inventor： Ningsheng Xu ,  Shaozhi Deng ,  Juncong She ,  Jun Chen

IPC: B81B1/00 ,  B81C1/00 ,  B05D1/36 ,  B05D5/00

CPC classification number: B81C1/00111 ,  B81B2201/055 ,  B82Y30/00

Abstract: This invention relates to a method for locally depositing coatings on microtip apex. The technical procedures are listed as following. (1) Using parting layer to cover the tip body and only leave the apex protruded A parting layer was deposited on the entire microtip sample surface. The film thickness is thicker than the height of microtip. By thinning the parting layer, the tip apex was exposed, but the body remains being covered. The height of the exposed tip apex can be controlled by adjusting the thinning parameters. (2) Surface cleaning and passivation treatment Surface cleaning and passivation treatment are performed on the apex of the microtip according to actual needs. (3) Coating Based on actual needs, a selected functional thin film is coated on the microtip sample. (4) Remove the parting layer to form the locally coated tip By using an etchant that only react with the parting layer but not the microtip and the coated material, the parting layer can selectively removed, leave a locally coated microtip. Using the aforementioned method, it is able to perform surface cleaning and locally thin film depositing on microtip apex.

Abstract translation: 本发明涉及一种在微尖端上局部沉积涂层的方法。 技术手续如下。 （1）使用分离层覆盖顶端体并且只留下顶点突出的A分离层沉积在整个微尖端样品表面上。 膜厚比微尖的厚度厚。 通过使分离层变薄，尖端尖端被暴露，但是身体保持被覆盖。 可以通过调整稀化参数来控制暴露顶端顶点的高度。 （2）表面清洁和钝化处理根据实际需要，在微尖端上进行表面清洁和钝化处理。 （3）涂层根据实际需要，在微尖端样品上涂覆选定的功能性薄膜。 （4）去除分层以形成局部涂覆的尖端通过使用仅与分离层反应但不与微尖端和涂覆材料反应的蚀刻剂，可以选择性地除去分层，留下局部涂覆的微尖端。 使用上述方法，能够在微尖端上进行表面清洁和局部薄膜沉积。

公开(公告)号：US06815360B1

公开(公告)日：2004-11-09

申请号：US09744152

申请日：2001-02-08

Applicant: Leigh T Canham ,  Timothy I Cox ,  Christopher L. Reeves

Inventor： Leigh T Canham ,  Timothy I Cox ,  Christopher L. Reeves

IPC: H01L21302

CPC classification number: B81C1/00111 ,  A61B5/14514 ,  A61B5/150022 ,  A61B5/150282 ,  A61B5/150396 ,  A61B5/150969 ,  A61B5/150984 ,  B81B2201/055 ,  B81C1/00087

Abstract: A method of providing a microprojection (180) on the surface of a first material, the microprojection having a base portion adjacent the first material and a remote, or a tip portion, and a duct (182) at least in a region of the tip portion and the method comprising micro-machining the first material to provide the micro-projection duct. Various uses of the microprojection are also disclosed including light guides and cuvettes from micro-analytical systems, microneedles for transdermal fluid delivery or the like.

Abstract translation: 一种在第一材料的表面上提供微喷射体（180）的方法，所述微喷射体具有与所述第一材料相邻的基部和至少在所述尖端的区域中的远端或尖端部分和管道（182） 部分，并且该方法包括微加工第一材料以提供微投影管。 还公开了微喷射体的各种用途，包括来自微分析系统的光导和比色皿，用于透皮流体输送的微针等。

公开(公告)号：US06511463B1

公开(公告)日：2003-01-28

申请号：US09442827

申请日：1999-11-18

Applicant: Robert L. Wood ,  Henry A. Wynands ,  Karen W. Markus

Inventor： Robert L. Wood ,  Henry A. Wynands ,  Karen W. Markus

IPC: A61M500

CPC classification number: B81C99/0085 ,  A61B5/14514 ,  A61B5/150022 ,  A61B5/150282 ,  A61B5/150984 ,  A61M37/0015 ,  A61M2037/003 ,  A61M2037/0053 ,  B81B2201/055 ,  Y10T29/302 ,  Y10T29/49222

Abstract: Microneedle arrays are fabricated by providing a sacrificial mold including a substrate and an array of posts, preferably solid posts, projecting therefrom. A first material is coated on the sacrificial mold including on the substrate and on the array of posts. The sacrificial mold is removed to provide an array of hollow tubes projecting from a base. The inner and outer surfaces of the array of hollow tubes are coated with a second material to create the array of microneedles projecting from the base. The sacrificial mold may be fabricated by fabricating a master mold, including an array of channels that extend into the master mold from a face thereof. A third material is molded into the channels and on the face of the master mold, to create the sacrificial mold. The sacrificial mold then is separated from the master mold. Alternatively, wire bonding may be used to wire bond an array of wires to a substrate to create the sacrificial mold. The first material preferably is coated on the sacrificial mold by plating. Prior to plating, a plating base preferably is formed on the sacrificial mold including on the substrate and on the array of posts. The inner and outer surfaces of the array of hollow tubes preferably are coated with the second material by overplating the second material on the inner and outer surfaces of the array of hollow tubes.

Abstract translation: 微针阵列通过提供包括基底和从其突出的柱的阵列（优选固体柱）的牺牲模具来制造。 第一材料涂覆在牺牲模具上，包括在基板上和柱阵列上。 去除牺牲模具以提供从基部突出的中空管阵列。 中空管阵列的内表面和外表面涂覆有第二材料以产生从基底突出的微针阵列。 牺牲模具可以通过制造主模具来制造，该模具包括从其表面延伸到主模具中的通道阵列。 将第三种材料模制到通道中并在母模的表面上，以形成牺牲模具。 然后将牺牲模具与主模具分离。 或者，引线接合可用于将线阵列引线接合到基底以产生牺牲模。 第一种材料优选通过电镀涂覆在牺牲模具上。 在电镀之前，优选在包括在基板和柱阵列上的牺牲模具上形成镀覆基底。 优选地，中空管阵列的内表面和外表面通过在中空管阵列的内表面和外表面上的第二材料的上镀敷而涂覆有第二材料。

公开(公告)号：US20020193754A1

公开(公告)日：2002-12-19

申请号：US09880377

申请日：2001-06-13

Inventor： Steve T. Cho

IPC: A61M005/32

CPC classification number: B81C1/00111 ,  A61B5/14514 ,  A61B5/150022 ,  A61B5/150221 ,  A61B5/150282 ,  A61B5/150748 ,  A61B5/15087 ,  A61B5/150969 ,  A61B5/150984 ,  A61B5/157 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0038 ,  A61M2037/0053 ,  B81B2201/055

Abstract: The present invention provides a microneedle incorporating a base that is broad relative to a height of the microneedle, to minimize breakage. The microneedle further includes a fluid channel and a beveled non-coring tip. Preferably arrays of such microneedles are fabricated utilizing conventional semiconductor derived micro-scale fabrication techniques. A dot pattern mask is formed on an upper surface of a silicon substrate, with each orifice of the dot pattern mask corresponding to a desired location of a microneedle. Orifices are formed that pass completely through the substrate by etching. A nitride pattern mask is formed to mask all areas in which a nitride layer is not desired. A nitride layer is then deposited on the bottom of the silicon substrate, on the walls of the orifice, and on the top of the silicon substrate around the periphery of the orifice. The nitride layer around the periphery of the orifice is offset somewhat, such that one side of the orifice has a larger nitride layer. Anisotropic etching is used to remove a substantial portion of the substrate, creating a plurality of angular, blunt, and generally pyramidal-shaped microneedles. A subsequent removal of the nitride layer, followed by an isotropic etching step, softens and rounds out the blunt angular microneedles, providing generally conical-shaped microneedles. The uneven nitride layer adjacent the orifice ensures that the microneedles will include a beveled tip. Such microneedle arrays are preferably incorporated into handheld diagnostic and drug delivery systems.

Abstract translation: 本发明提供了一种结合了相对于微针的高度宽的基底的微针，以使破损最小化。 微针还包括流体通道和倾斜的非取心尖端。 优选地，使用常规的半导体衍生的微尺度制造技术制造这种微针的阵列。 在硅基板的上表面上形成点阵图案掩模，点图案掩模的每个孔口对应于微针的期望位置。 形成通过蚀刻完全通过基板的孔。 形成氮化物图案掩模以掩盖不需要氮化物层的所有区域。 然后将氮化物层沉积在硅衬底的底部，孔的壁上，以及围绕孔的周边的硅衬底的顶部上。 围绕孔的周边的氮化物层稍微偏移，使得孔的一侧具有较大的氮化物层。 使用各向异性蚀刻去除基本部分的大部分，产生多个角，钝，通常为锥形的微针。 随后去除氮化物层，随后进行各向同性的蚀刻步骤，软化和圆化钝角微针，提供大致锥形的微针。 邻近孔口的不均匀氮化物层确保了微针将包括一个倾斜尖端。 这种微针阵列优选并入手持诊断和药物输送系统中。

公开(公告)号：US06471903B2

公开(公告)日：2002-10-29

申请号：US09956520

申请日：2001-09-19

Applicant: Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

Inventor： Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov ,  Vladimir Gartstein ,  Grover David Owens

IPC: B29C3342

CPC classification number: B29C51/082 ,  A61M37/00 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  B26F1/24 ,  B29C33/0033 ,  B29C33/42 ,  B29C37/0053 ,  B29C45/2628 ,  B29C51/00 ,  B29C2059/023 ,  B29L2031/7544 ,  B29L2031/756 ,  B81B2201/055 ,  B81C1/00111 ,  B81C2201/036

Abstract: An array of hollow microneedles is constructed of molded plastic, in which a micro-machining technique is used to fabricate the molds used in a plastic microforming process. The molds are detachable and can be re-used. The preferred process for making the plastic arrays of microneedles is a microinjection technique. In the microinjection method, a molten plastic substance is injected between two micro-machined molds that contain microhole and micropillar arrays. Once the desired shape of the microneedle array has been formed, the mold and the plastic material are cooled down. Next, the molds are separated and the plastic microneedle array is detached from the mold structures.

Abstract translation: 中空微针阵列由模制塑料构成，其中使用微加工技术来制造在塑料微成形过程中使用的模具。 模具是可拆卸的，可以重新使用。 用于制造微针的塑料阵列的优选方法是显微注射技术。 在显微注射方法中，将熔融塑料物质注入包含微孔和微柱阵列的两个微加工模具之间。 一旦已经形成所需的微针阵列形状，就将模具和塑料材料冷却下来。 接下来，模具被分离，并且塑料微针阵列与模具结构分离。

公开(公告)号：US20020133129A1

公开(公告)日：2002-09-19

申请号：US09808534

申请日：2001-03-14

Inventor： Francisco Arias ,  Faiz Feisal Sherman ,  Grover David Owens

IPC: A61B017/20 ,  B29C067/00

CPC classification number: A61B5/1411 ,  A61B5/14514 ,  A61B5/150022 ,  A61B5/150282 ,  A61B5/150419 ,  A61B5/150984 ,  A61M37/0015 ,  A61M2037/0038 ,  A61M2037/0053 ,  B81B2201/055 ,  B81C1/00111 ,  B81C2201/034

Abstract: A method for manufacturing microneedle structures is disclosed using soft lithography and photolithography, in which micromold structures made of a photoresist material or PDMS are created. The micromold manufacturing occurs quite quickly, using inexpensive materials and processes. Once the molds are available, using moldable materials such as polymers, microneedle arrays can be molded or embossed in relatively fast procedures. In some cases a sacrificial layer is provided between the forming micromold and its substrate layer, for ease of separation. The microneedles themselves can be solid projections, hollow nullmicrotubes,null or shallow nullmicrocups.null Electrodes can be formed on the microneedle arrays, including individual electrodes per hollow microtube.

Abstract translation: 公开了使用软光刻和光刻技术制造微针结构的方法，其中制造由光致抗蚀剂材料或PDMS制成的微型结构。 使用廉价的材料和工艺，微型制造相当快速地发生。 一旦模具可用，使用可模塑材料如聚合物，微针阵列可以以相对较快的程序模制或压花。 在一些情况下，为了易于分离，在成形微胶体与其基底层之间提供牺牲层。 微针本身可以是固体突起，中空的“微管”或浅的“微型杯”。 电极可以形成在微针阵列上，包括每个中空微管的单个电极。

公开(公告)号：US20020053756A1

公开(公告)日：2002-05-09

申请号：US09974829

申请日：2001-10-12

Applicant: Becton Dickinson and Company

Inventor： Kenneth G. Powell ,  Larry A. Monahan ,  Burton H. Sage JR.

IPC: B29C033/38 ,  B29C033/56 ,  B29C043/02 ,  B29C045/37

CPC classification number: B29C33/405 ,  A61M37/0015 ,  A61M2037/0046 ,  A61M2037/0053 ,  B29C33/424 ,  B29C45/372 ,  B29C2045/0094 ,  B29K2883/00 ,  B29L2031/7544 ,  B29L2031/756 ,  B81B2201/055 ,  B81C1/00111 ,  B81C2201/034

Abstract: A device, preferably a micro-device, is molded from a plastic material by injection molding, compression molding or embossing. A microabrader can be molded having microneedles for abrading the stratum corneum of the skin to form an abraded site in the tissue for enhancing drug delivery. The micro-device is molded using a mold assembly having a silicon molding surface. The silicon molding surface can include a recess corresponding to the desired shape and length of the microneedles. The silicon molding surface enables micron and submicron size features to be molded from polymeric materials without the polymeric material adhering to the mold surface. Micro-devices having molded features having micron and submicron dimensions can be rapidly produced without the use of a release agent.

Abstract translation: 一种装置，优选一种微型装置，通过注塑，压塑或压花由塑料材料模制。 微型造型机可以模制成具有用于研磨皮肤角质层的微针，以在组织中形成用于增强药物递送的磨损部位。 使用具有硅模制表面的模具组件来模制微型装置。 硅成型表面可以包括对应于所需形状和长度的微针的凹部。 硅成型表面使得微米和亚微米尺寸的特征能够由聚合物材料模制而不会使聚合材料粘附到模具表面。 具有微米和亚微米尺寸的模制特征的微型装置可以在不使用脱模剂的情况下快速生产。

公开(公告)号：US06379324B1

公开(公告)日：2002-04-30

申请号：US09328947

申请日：1999-06-09

Applicant: Vladimir Gartstein ,  Dragan Danilo Nebrigic ,  Grover David Owens ,  Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov

Inventor： Vladimir Gartstein ,  Dragan Danilo Nebrigic ,  Grover David Owens ,  Faiz Feisal Sherman ,  Vadim Vladimirovich Yuzhakov

IPC: A61B1720

CPC classification number: B81C99/0085 ,  A61B5/14514 ,  A61B5/150022 ,  A61B5/150099 ,  A61B5/150282 ,  A61B5/150389 ,  A61B5/150412 ,  A61B5/150458 ,  A61B5/150969 ,  A61B5/150984 ,  A61M37/0015 ,  A61M2037/0023 ,  A61M2037/003 ,  A61M2037/0053 ,  B29L2031/7544 ,  B29L2031/756 ,  B81B2201/055

Abstract: A first embodiment microneedle array is constructed of silicon and silicon dioxide compounds using MEMS technology and standard microfabrication techniques to create hollow cylindrical individual microneedles. The resulting array of microneedles can penetrate with a small pressure through the stratum corneum of skin to either deliver drugs or to facilitate interstitial fluid sampling through the hollow microneedles into the epidermis. The delivery of drugs and sampling of fluids can be performed by way of passive diffusion (time release), instantaneous injection, or iontophoresis. In a second embodiment, an array of hollow (or solid) microneedles is constructed of plastic or some other type of molded or cast material. An electric field may be used to increase transdermal flow rate, and the microneedles can be effectively combined with the application of an electric field between an anode and cathode attached to the skin which causes a low-level electric current. As a drug delivery system, the microneedle array includes electrodes that apply an electric potential to the skin between the electrode locations. One of the electrode assemblies is filled with an ionized drug, and the charged drug molecules move into the body due to the applied electric potential. As a body-fluid sampling system, the microneedle array also includes electrodes to assist in moving fluid from the body into a receiving chamber, and which further includes a bioelectrochemical sensor to measure the concentration of a particular substance.

Abstract translation: 第一实施例微针阵列由硅和二氧化硅化合物构成，使用MEMS技术和标准微加工技术来制造中空圆柱形单个微针。 所得的微针阵列可以通过皮肤的角质层穿透小的压力，以递送药物或促进通过空心微针进入表皮的间质液取样。 可以通过被动扩散（时间释放），瞬时注射或离子电渗法进行药物的输送和液体取样。 在第二实施例中，中空（或固体）微针的阵列由塑料或其它类型的模制或铸造材料构成。 可以使用电场来增加透皮流速，并且可以将微针与附着在皮肤上的阳极和阴极之间的电场的施加有效地组合，这导致低电平电流。 作为药物递送系统，微针阵列包括在电极位置之间向皮肤施加电位的电极。 电极组件中的一个填充有电离药物，并且带电药物分子由于施加的电位而进入体内。 作为体液采样系统，微针阵列还包括有助于将流体从身体移动到接收室中的电极，并且还包括用于测量特定物质浓度的生物电化学传感器。