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    Microchip drug delivery devices
    21.
    发明授权
    Microchip drug delivery devices 失效
    Microchip药物输送装置

    公开(公告)号：US5797898A

    公开(公告)日：1998-08-25

    申请号：US675375

    申请日：1996-07-02

    申请人： John T. Santini, Jr. ,  Michael J. Cima ,  Robert S. Langer

    发明人： John T. Santini, Jr. ,  Michael J. Cima ,  Robert S. Langer

    IPC分类号： A61K9/00 ,  A61K9/52 ,  A61M37/00 ,  A61K9/22

    CPC分类号： A61K9/0009 ,  A61K9/0097 ,  A61M2205/0244 ,  A61M37/00

    摘要： Microchips are provided, which control both the rate and time of release of multiple chemical substances and which allow for the release of a wide variety of molecules in either a continuous or pulsatile manner. In all of the preferred embodiments, a material that is impermeable to the drugs or other molecules to be delivered and the surrounding fluids is used as the substrate. Reservoirs are etched into the substrate using either chemical (wet) etching or ion beam (dry) etching techniques well known in the field of microfabrication. Hundreds to thousands of reservoirs can be fabricated on a single microchip using these techniques. The molecules to be delivered are inserted into the reservoirs by injection or spin coating methods in their pure form or in a release system. Exemplary release systems include polymers and polymeric matrices, non-polymeric matrices, and other excipients or diluents. The physical properties of the release system control the rate of release of the molecules. The reservoirs can contain multiple drugs or other molecules in variable dosages. The filled reservoirs can be capped with materials that either degrade or allow the molecules to diffuse passively out of the reservoir over time or materials that oxidize and dissolve upon application of an electric potential. Release from an active device can be controlled by a preprogrammed microprocessor, remote control, or by biosensors.

    摘要翻译： 提供微芯片，其控制多种化学物质的释放速率和时间，并且允许以连续或脉动方式释放多种分子。 在所有优选的实施方案中，将待递送的药物或其它分子和周围流体不可渗透的材料用作基底。 使用在微细加工领域熟知的化学（湿）蚀刻或离子束（干）蚀刻技术将储层蚀刻到基底中。 使用这些技术，可以在单个微芯片上制造数百到数千个储层。 通过注射或旋涂方法将要输送的分子以纯形式或释放系统插入储存器中。 示例性的释放系统包括聚合物和聚合物基质，非聚合物基质和其它赋形剂或稀释剂。 释放系统的物理性质控制分子的释放速率。 储层可以含有多种药物或其他可变剂量的分子。 填充的储存器可以被降解的材料封盖，或允许分子随时间被动地扩散到储存器中，或者在施加电势时氧化和溶解的材料。 从有源设备释放可以由预编程的微处理器，遥控器或生物传感器控制。

    Hermetically sealed microchip reservoir devices
    23.
    发明授权
    Hermetically sealed microchip reservoir devices 有权
    密封微芯片油藏装置

    公开(公告)号：US07497846B2

    公开(公告)日：2009-03-03

    申请号：US11005391

    申请日：2004-12-06

    申请人： Scott A. Uhland ,  Benjamin F. Polito ,  Stephen J. Herman ,  John T. Santini, Jr. ,  John M. Maloney

    发明人： Scott A. Uhland ,  Benjamin F. Polito ,  Stephen J. Herman ,  John T. Santini, Jr. ,  John M. Maloney

    IPC分类号： A61M5/00 ,  A61K9/22

    CPC分类号： A61K9/0097

    摘要： Devices are provided for the controlled exposure or release of contents stored in hermetically sealed reservoirs. The devices comprise a primary substrate having a front side and a back side, and including one or more hermetic sealing materials; a plurality of reservoirs in the primary substrate positioned between the front side and the back side; reservoir contents, which comprise chemical molecules (such as drugs) or a secondary device (such as a glucose sensor), located inside the reservoirs; a hermetic sealing substrate having a surface composed of one or more hermetic sealing materials; and a hermetic seal formed between and joining the primary substrate and the hermetic sealing substrate, wherein the hermetic seal independently seals the reservoirs.

    摘要翻译： 提供了用于控制曝光或释放存储在密封储存器中的内容物的装置。 这些装置包括具有前侧和后侧的主基板，并且包括一个或多个密封材料; 位于前侧和后侧之间的主要基底中的多个储存器; 包括化学分子（如药物）或位于储存器内部的次级装置（如葡萄糖传感器）的储存器内容物; 具有由一种或多种密封材料构成的表面的气密密封基材; 以及形成在主基板和气密密封基板之间并与其接合的气密密封件，其中气密密封独立地密封储存器。

    Methods for hermetically sealing microchip reservoir devices
    24.
    发明授权
    Methods for hermetically sealing microchip reservoir devices 有权
    密封微芯片储液装置的方法

    公开(公告)号：US06827250B2

    公开(公告)日：2004-12-07

    申请号：US10184259

    申请日：2002-06-28

    申请人： Scott A. Uhland ,  Benjamin F. Polito ,  Stephen J. Herman ,  John T. Santini, Jr. ,  John M. Maloney

    发明人： Scott A. Uhland ,  Benjamin F. Polito ,  Stephen J. Herman ,  John T. Santini, Jr. ,  John M. Maloney

    IPC分类号： B23K106

    CPC分类号： A61K9/0097

    摘要： Methods are provided for hermetically sealing the reservoirs of microchip devices and for hermetically sealing the substrate assemblies in a hermetic packaging structure. In one embodiment, the method comprises (1) providing a primary substrate having a front side and a back side, the substrate comprising a plurality of reservoirs positioned between the front side and the back side, each reservoir being loaded with molecules or a secondary device for controlled release or exposure, the reservoirs having at least one opening in need of sealing, the primary substrate including one or more hermetic sealing materials; (2) providing a hermetic sealing substrate having a surface composed of one or more hermetic sealing materials; (3) positioning the hermetic sealing substrate over the reservoir openings and contacting said hermetic sealing materials of the primary substrate with said hermetic sealing materials of the hermetic sealing substrate; and (4) applying energy or a mechanical force to the contacted sealing materials effective to form a hermetic seal between the hermetic sealing substrate and the primary substrate to hermetically seal the reservoir openings.

    摘要翻译： 提供了用于气密地密封微芯片装置的储存器的方法，以及用于密封密封封装结构中的基板组件。 在一个实施例中，该方法包括（1）提供具有前侧和后侧的主基底，所述基底包括位于前侧和后侧之间的多个储存器，每个储存器装载有分子或辅助装置 为了控制释放或暴露，储存器具有至少一个需要密封的开口，主基底包括一个或多个气密密封材料; （2）提供具有由一种或多种密封材料构成的表面的气密密封基材; （3）将气密密封基板定位在储存器开口上，并使主基板的气密密封材料与气密密封基板的气密密封材料接触; 和（4）将能量或机械力施加到接触的密封材料上，以有效地在气密密封基底和初级基底之间形成气密密封，从而气密地密封储层开口。

    Micro-reservoir osmotic release systems and microtube array device
    26.
    发明授权
    Micro-reservoir osmotic release systems and microtube array device 有权
    微储层渗透释放系统和微管阵列装置

    公开(公告)号：US07534241B2

    公开(公告)日：2009-05-19

    申请号：US10668573

    申请日：2003-09-23

    申请人： Jonathan R. Coppeta ,  John T. Santini, Jr. ,  Scott A. Uhland

    发明人： Jonathan R. Coppeta ,  John T. Santini, Jr. ,  Scott A. Uhland

    IPC分类号： A61K9/22

    CPC分类号： A61M31/002 ,  A61K9/0004 ,  A61K9/0024 ,  A61K9/0097 ,  A61M5/141 ,  A61M5/14276 ,  A61M5/14526 ,  A61M31/00 ,  A61M37/00 ,  A61M37/0015 ,  A61M2005/14513 ,  A61M2037/0023 ,  A61M2205/0244 ,  A61M2205/0266

    摘要： Devices and methods are provided for controlled release of chemical molecules, such as drugs. One device comprises a plurality of reservoirs; a rupturable covering, such as a thin metal film, enclosing a first end of each reservoir; a release formulation in each reservoir comprising chemical molecules for release; an expanding material layer in each reservoir; and a semi-permeable membrane enclosing a second end of each reservoir distal the release formulation, the semi-permeable membrane being operable to permit selected molecules (e.g., water) from outside the reservoir to diffuse to the expanding material layer to expand the expanding material layer and displace the release formulation in an amount effective rupture the rupturable membrane and discharge the release formulation. The device may further comprises a reservoir cap covering semi-permeable membrane and means for selectively disintegrating the reservoir cap to initiate diffusion of fluid molecules from outside the reservoir and through the semi-permeable membrane.

    摘要翻译： 提供了用于控制释放化学分子（例如药物）的装置和方法。 一个装置包括多个储存器; 诸如薄金属膜的破裂覆盖物，其包围每个储存器的第一端; 每个储存器中的释放制剂包含用于释放的化学分子; 每个储存器中的膨胀材料层; 以及半透膜，其围绕所述释放制剂封闭每个储存器的第二端，所述半透膜可操作以允许从所述储存器外部的选定分子（例如水）扩散到所述膨胀材料层以膨胀所述膨胀材料 并将释放制剂置于有效破裂可破裂膜并排出释放制剂的量。 装置还可以包括覆盖半透膜的储存器盖和用于选择性地分解储存器盖以启动流体分子从储存器外部并通过半透膜的装置的装置。

    Fabrication methods and structures for micro-reservoir devices
    27.
    发明授权
    Fabrication methods and structures for micro-reservoir devices 有权
    微储层装置的制造方法和结构

    公开(公告)号：US07413846B2

    公开(公告)日：2008-08-19

    申请号：US10988667

    申请日：2004-11-15

    申请人： John M. Maloney ,  Zouhair Sbiaa ,  John T. Santini, Jr. ,  Norman F. Sheppard, Jr. ,  Scott A. Uhland

    发明人： John M. Maloney ,  Zouhair Sbiaa ,  John T. Santini, Jr. ,  Norman F. Sheppard, Jr. ,  Scott A. Uhland

    IPC分类号： G03F7/20

    CPC分类号： B01L3/50853 ,  A61K9/0024 ,  A61K9/0097 ,  B01L2200/12 ,  B01L2300/0819 ,  B01L2400/0677

    摘要： Methods are provided for making a multi-reservoir device comprising (i) patterning one or more photoresist layers on a substrate; (ii) depositing onto the substrate at least one metal layer by a sputtering process to form a plurality of reservoir caps and conductive traces; (iii) removing the photoresist layers using a liftoff process; (iv) forming a plurality of reservoirs in the substrate; (v) loading each reservoir with reservoir contents (such as a drug or sensor); and (vi) sealing each reservoir. Optionally, the reservoir cap comprises a first conductive metal layer coated with one or more protective noble metal films. To enhance the resistance of the substrate (e.g., a silicon substrate) to etching in vivo, the interior sidewalls of the reservoirs optionally can include a protective coating (e.g., gold, platinum, carbon, silicon carbide, silicon dioxide, and platinum silicide), or sidewalls comprising silicon can be doped with boron or another impurity.

    摘要翻译： 提供了用于制造多贮存器器件的方法，包括（i）在衬底上图案化一个或多个光致抗蚀剂层; （ii）通过溅射工艺在衬底上沉积至少一个金属层以形成多个储存器盖和导电迹线; （iii）使用剥离工艺除去光致抗蚀剂层; （iv）在所述基板中形成多个储存器; （v）向每个储存器装载储存器内容物（例如药物或传感器）; 和（vi）密封每个储存器。 可选地，储存器盖包括涂覆有一个或多个保护性贵金属膜的第一导电金属层。 为了增强衬底（例如，硅衬底）在体内蚀刻的电阻，存储器的内侧壁任选地可以包括保护涂层（例如金，铂，碳，碳化硅，二氧化硅和硅化铂） ，或者包含硅的侧壁可以掺杂硼或另一种杂质。

    Thermally-activated microchip chemical delivery devices
    29.
    发明授权
    Thermally-activated microchip chemical delivery devices 有权
    热敏微芯片化学输送装置

    公开(公告)号：US06527762B1

    公开(公告)日：2003-03-04

    申请号：US09638109

    申请日：2000-08-11

    申请人： John T. Santini, Jr. ,  Michael J. Cima ,  Scott Albert Uhland

    发明人： John T. Santini, Jr. ,  Michael J. Cima ,  Scott Albert Uhland

    IPC分类号： A61K911

    CPC分类号： B01L3/50853 ,  A61K9/0009 ,  A61K9/0024 ,  A61K9/0097 ,  B01L2300/0819 ,  B01L2400/0677

    摘要： Microchip delivery devices are provided that control both the rate and time of release of molecules, wherein the device includes a substrate, at least one reservoir in the substrate containing the molecules, and a reservoir cap positioned on the reservoir over the molecules, wherein the molecules are released from the reservoir upon heating or cooling the device or a portion thereof sufficient to rupture the reservoir cap. In a preferred embodiment, the device includes a resistor integrated into the reservoir or mounted near the reservoir, which upon application of an electric current through the resistor, causes at least one of the contents of the reservoir to thermally expand, vaporize, phase change, or undergo a thermally driven reaction, such that the reservoir cap ruptures due to mechanical stress. In another preferred embodiment, application of an electric current to a resistor located on or near the reservoir cap causes the cap to expand, contract, or undergo a phase change that results in the rupture of the reservoir cap. The reservoirs can contain multiple drugs or other molecules in variable dosages. Each of the reservoirs of a single microchip can contain different molecules and/or different amounts and concentrations, which can be released independently.

    摘要翻译： 提供Microchip输送装置，其控制释放分子的速率和时间，其中所述装置包括底物，所述基质中含有所述分子的至少一个储存器和位于所述分子上的所述储存器上的储存器盖，其中所述分子 在加热或冷却装置或其一部分足以破坏储存器盖时从储存器释放。 在优选实施例中，该装置包括集成在储存器中或安装在储存器附近的电阻器，当施加电流通过电阻器时，储存器的至少一个内容物热膨胀，蒸发，相变， 或经历热驱动反应，使得储存器盖由于机械应力而破裂。 在另一个优选实施例中，将电流施加到位于储存器盖上或附近的电阻器使得盖膨胀，收缩或经历相变，导致储存器盖的破裂。 储层可以含有多种药物或其他可变剂量的分子。 单个微芯片的每个储存器可以包含不同的分子和/或不同的量和浓度，其可以独立释放。