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1. 发明授权

US06692456B1 Apparatus for microporation of biological membranes using thin film tissue interface devices, and method therefor 有权
标题翻译：用于使用薄膜组织界面装置微生物生物膜的装置及其方法
公开(公告)号：US06692456B1
公开(公告)日：2004-02-17
申请号：US09590787
申请日：2000-06-08
申请人： Jonathan A. Eppstein , Michael R. Hatch , Joseph Papp
发明人： Jonathan A. Eppstein , Michael R. Hatch , Joseph Papp
IPC分类号： A61B1720
CPC分类号： A61N1/30 , A61B10/0045 , A61B17/205 , A61B2010/008 , A61B2017/00761 , A61K41/0047 , A61M37/0015 , A61M2005/3022 , A61M2037/0007 , A61M2037/0023 , A61M2037/0038 , A61M2037/0053 , A61N1/0424 , A61N1/044 , A61N1/0452 , A61N1/0456 , A61N1/0476 , A61N1/306 , A61N1/327
摘要： The invention provides for improved devices and methods for forming openings in a biological membrane for delivering substances into an animal through the biological membrane for treatment applications, or extracting substances from the animal through the biological membrane for monitoring or other diagnosis applications and for increased transmembrane flux.
摘要翻译：本发明提供了用于在生物膜中形成开口的改进的装置和方法，用于通过生物膜将物质输送到动物中用于治疗应用，或者通过用于监测或其他诊断应用的生物膜从动物提取物质，以及增加跨膜通量。

2. 发明授权

US06730028B2 Controlled removal of biological membrane by pyrotechnic charge for transmembrane transport 有权
标题翻译：通过用于跨膜运输的烟火装置控制生物膜的去除
公开(公告)号：US06730028B2
公开(公告)日：2004-05-04
申请号：US10040066
申请日：2001-10-29
申请人： Jonathan A. Eppstein , Michael R. Hatch , Joseph Papp , Mark L. Faupel , Krishna Kumar
发明人： Jonathan A. Eppstein , Michael R. Hatch , Joseph Papp , Mark L. Faupel , Krishna Kumar
IPC分类号： A61B500
CPC分类号： A61N1/30 , A61B10/0045 , A61B17/205 , A61B2010/008 , A61B2017/00761 , A61K41/0047 , A61M5/2046 , A61M37/00 , A61M2037/0007
摘要： A method and device for forming artificial openings in a biological membrane with a pyrotechnic charge that is exploded in a controlled manner in proximity of the biological membrane to form the artificial opening(s) therein. The method and device are useful in connection with transdermal delivery and monitoring applications.
摘要翻译：一种在生物膜中形成人造开口的方法和装置，其中烟火电荷以受控的方式在生物膜附近分解以在其中形成人造开口。该方法和装置可用于透皮递送和监测应用。

3. 发明授权

US06352506B1 Controlled removal of biological membrane by pyrotechnic charge for transmembrane transport 有权
公开(公告)号：US06352506B1
公开(公告)日：2002-03-05
申请号：US09353130
申请日：1999-07-14
申请人： Jonathan A. Eppstein , Michael R. Hatch , Joseph Papp , Mark L. Faupel , Krishna Kumar
发明人： Jonathan A. Eppstein , Michael R. Hatch , Joseph Papp , Mark L. Faupel , Krishna Kumar
IPC分类号： A61B500
CPC分类号： A61N1/30 , A61B10/0045 , A61B17/205 , A61B2010/008 , A61B2017/00761 , A61K41/0047 , A61M5/2046 , A61M37/00 , A61M2037/0007
摘要： A method and device for forming artificial openings in a biological membrane with a pyrotechnic charge that is exploded in a controlled manner in proximity of the biological membrane to form the artificial opening(s) therein. The method and device are useful in connection with transdermal delivery and monitoring applications.

4. 发明授权

US5885211A Microporation of human skin for monitoring the concentration of an analyte 失效
标题翻译：用于监测分析物浓度的人皮肤的微孔
公开(公告)号：US5885211A
公开(公告)日：1999-03-23
申请号：US776863
申请日：1997-09-05
申请人： Jonathan A. Eppstein , Michael R. Hatch , Difei Yang
发明人： Jonathan A. Eppstein , Michael R. Hatch , Difei Yang
IPC分类号： A61B5/00 , A61B10/00 , A61B17/00 , A61B17/32 , A61B18/20 , A61K41/00 , A61K49/22 , A61M37/00
CPC分类号： A61B5/681 , A61B10/0045 , A61B5/14514 , A61B5/1486 , A61K41/0047 , A61K49/22 , A61M37/0092 , A61B17/3203 , A61B18/20 , A61B18/203 , A61B2017/00172 , A61B2017/00761 , A61B2017/00765 , A61B2018/00452 , A61B2018/0047 , A61B2562/0295 , A61M2037/0007
摘要： A method of enhancing the permeability of the skin to an analyte for diagnostic purposes or to a drug for therapeutic purposes is described utilizing microporation and optionally sonic energy and a chemical enhancer. If selected, the sonic energy may be modulated by means of frequency modulation, amplitude modulation, phase modulation, and/or combinations thereof. Microporation is accomplished by (a) ablating the stratum corneum by localized rapid heating of water such that such water is vaporized, thus eroding the cells; (b) puncturing the stratum corneum with a micro-lancet calibrated to form a micropore of up to about 1000 .mu.m in diameter; (c) ablating the stratum corneum by focusing a tightly focused beam of sonic energy onto the stratum corneum; (d) hydraulically puncturing the stratum corneum with a high pressure jet of fluid to form a micropore of up to about 1000 .mu.m in diameter, or (e) puncturing the stratum corneum with short pulses of electricity to form a micropore of up to about 1000 .mu.m in diameter. A dye with an absorption maximum matched to the wavelength of a pulsed light source can be absorbed into the stratum corneum to concentrate the energy of the pulsed light source and aid in ablation of the stratum corneum. Alternatively, a hot wire can be caused to contact the stratum corneum.
摘要翻译： PCT No.PCT / US96 / 13865 Sec。 371日期：1997年9月5日 102（e）1997年9月5日PCT PCT 1996年8月29日PCT公布。公开号WO97 / 07734 日期1997年3月6日利用微孔和任选的声能和化学增强剂描述了增强皮肤对诊断目的的分析物或用于治疗目的的药物的渗透性的方法。如果选择，则可以通过频率调制，幅度调制，相位调制和/或其组合来调制声能。通过（a）通过局部快速加热水来消融角质层，使得这种水被蒸发，从而侵蚀细胞来实现微孔化; （b）用经过校准的微型刺血针刺穿角质层以形成直径约达1000微米的微孔; （c）通过将紧密聚焦的声能束聚焦在角质层上来消融角质层; （d）用高压喷射流体水力刺穿角质层以形成直径达约1000μm的微孔，或（e）以短脉冲电穿刺角质层以形成高达约直径1000亩。具有与脉冲光源的波长匹配的吸收最大值的染料可以被吸收到角质层中以集中脉冲光源的能量并有助于消除角质层。或者，可以使热丝接触角质层。

5. 发明授权

US06951411B1 Light beam generation, and focusing and redirecting device 有权
标题翻译：光束产生，聚焦和重定向装置
公开(公告)号：US06951411B1
公开(公告)日：2005-10-04
申请号：US10018913
申请日：2000-06-15
申请人： Krishna S. Kumar , Danny F. Lincoln , Jonathan A. Eppstein , Michael R. Hatch
发明人： Krishna S. Kumar , Danny F. Lincoln , Jonathan A. Eppstein , Michael R. Hatch
IPC分类号： A61B17/00 , A61B18/20 , F21V14/06
CPC分类号： A61B18/20 , A61B2017/00765 , A61B2018/20351
摘要： An improved light beam generation and focusing device (15, 50) has a light source (16, 51) constructed and arranged to emit at least one beam of light (20), and a lens assembly (17, 19, 56) constructed and arranged to focus the at least one beam of light on a surface plane. The device is constructed and arranged to sequentially direct the at least one beam of light to at least two spaced locations (21, 21′) on the surface plane. The lens assembly comprises a collimating lens (17), and a spaced focusing lens (19).
摘要翻译：改进的光束产生和聚焦装置（15,50）具有构造和布置成发射至少一个光束（20）的光源（16,51），以及构成并构造的透镜组件（17,19,56）布置成将至少一束光聚焦在表面上。该装置被构造和布置成将至少一束光顺序地引导到表面上的至少两个间隔开的位置（21,21'）。透镜组件包括准直透镜（17）和间隔开的聚焦透镜（19）。

6. 发明授权

US06922578B2 Integrated poration, harvesting and analysis device, and method therefor 失效
标题翻译：综合栽培，收获和分析装置及其方法
公开(公告)号：US06922578B2
公开(公告)日：2005-07-26
申请号：US10671006
申请日：2003-09-25
申请人： Jonathan A. Eppstein , Mark A. Samuels , Michael R. Hatch
发明人： Jonathan A. Eppstein , Mark A. Samuels , Michael R. Hatch
IPC分类号： A61M37/00 , A61B5/00 , A61B10/00 , A61B17/00 , A61K41/00 , A61K45/00 , A61B5/05
CPC分类号： A61B5/15134 , A61B5/14514 , A61B5/14532 , A61B5/1455 , A61B5/150022 , A61B5/150068 , A61B5/150083 , A61B5/150099 , A61B5/150229 , A61B5/150358 , A61B5/15136 , A61B5/157 , A61B2010/008 , A61B2017/00172 , A61B2562/12 , A61K41/0047
摘要： An integrated device for poration of biological tissue, harvesting a biological fluid from the tissue, and analysis of the biological fluid. The device comprises a tissue-contacting layer having an electrically or optically heated probe to heat and conduct heat to the tissue to form at least one opening, such as a micropore to collect biological fluid from the opening, and a detecting layer responsive to the biological fluid to provide an indication of a characteristic of the biological fluid, such as the concentration of an analyte in interstitial fluid. In the embodiment in which, the probe comprises a photosensitizing assembly designed for the uniform application of a photosensitizing material, such as, for example, a dye or a pigment, to a tissue, e.g., the stratum comeum. In one embodiment, the photosensitizing assembly comprises photosensitizing material combined with a carrier, such as, for example, an adhesive or an ink, and the resulting combination is applied to a substrate, such as, for example, an inert polymeric substrate to form a photosensitizing assembly. In another embodiment, the photosensitizing assembly comprises photosensitizing material incorporated into a film-forming polymeric material.
摘要翻译：用于生物组织的装配，从组织收获生物流体和生物流体分析的综合装置。该装置包括具有电或光学加热的探针的组织接触层，以加热和传导热量到组织以形成至少一个开口，例如从孔开始收集生物流体的微孔，以及响应生物学的检测层流体以提供生物流体的特征的指示，例如间质液中分析物的浓度。在其中探针包括设计用于将光敏材料（例如染料或颜料）均匀施用于组织例如层状物的光敏组合物的实施方案中。在一个实施方案中，光敏组合物包含与载体（例如粘合剂或油墨）组合的光敏材料，并将所得组合物施加到基材上，例如惰性聚合物基材以形成光敏组装。在另一个实施方案中，光敏组合物包含掺入成膜聚合物材料中的光敏材料。

7. 发明授权

US06918874B1 Attribute compensation for analyte detection and/or continuous monitoring 失效
标题翻译：分析物检测和/或连续监测的属性补偿
公开(公告)号：US06918874B1
公开(公告)日：2005-07-19
申请号：US09786830
申请日：1999-09-10
申请人： Michael R. Hatch , Jonathan A. Eppstein , Stuart McRae
发明人： Michael R. Hatch , Jonathan A. Eppstein , Stuart McRae
IPC分类号： A61B5/00 , A61B10/00 , A61B17/00
CPC分类号： A61B5/14514 , A61B5/00 , A61B5/0002 , A61B5/14532 , A61B10/0045 , A61B2010/008
摘要： A system and method for detecting a measuring an analyte in a biological fluid of an animal. A harvesting device (10) is provided suitable for positioning on the surface of tissue of an animal to harvest biological fluid therefrom. The harvesting device (10) comprises an analyte sensor (50) positioned to be contacted by the harvested biological fluid and which generates a measurement signal representative of the analyte. At least one attribute sensor (40) is provided to measure an attribute associated with the biological fluid harvesting operation of the harvesting device (10) or the assay of the biological fluid, and which generates an attribute signal representative of the attribute. Adjustments are made to operational parameters of the harvesting device (10) based on the one or more attributes.
摘要翻译：一种用于检测测量动物的生物流体中的分析物的系统和方法。提供了适于定位在动物组织表面以从其收集生物流体的收获装置（10）。收集装置（10）包括分配物传感器（50），其被定位成与所采集的生物流体接触并产生代表分析物的测量信号。提供至少一个属性传感器（40）以测量与收获装置（10）的生物流体收集操作或生物流体的测定相关联的属性，并且其生成表示该属性的属性信号。基于一个或多个属性对收获装置（10）的操作参数进行调整。

8. 发明授权

US6142939A Microporation of human skin for drug delivery and monitoring applications 有权
标题翻译：人类皮肤微量药物输送和监测应用
公开(公告)号：US6142939A
公开(公告)日：2000-11-07
申请号：US208166
申请日：1998-12-09
申请人： Jonathan A. Eppstein , Michael R. Hatch , Difei Yang
发明人： Jonathan A. Eppstein , Michael R. Hatch , Difei Yang
IPC分类号： A61B5/00 , A61B10/00 , A61B17/00 , A61B17/32 , A61B18/20 , A61K41/00 , A61K49/22 , A61M37/00
CPC分类号： A61B5/681 , A61B10/0045 , A61B5/14514 , A61B5/1486 , A61K41/0047 , A61K49/22 , A61M37/0092 , A61B17/3203 , A61B18/20 , A61B18/203 , A61B2017/00172 , A61B2017/00761 , A61B2017/00765 , A61B2018/00452 , A61B2018/0047 , A61B2562/0295 , A61M2037/0007
摘要： A method of enhancing the permeability of the skin to an analyte for diagnostic purposes or to a drug for therapeutic purposes is described utilizing microporation and optionally sonic energy and a chemical enhancer. If selected, the sonic energy may be modulated by means of frequency modulation, amplitude modulation, phase modulation, and/or combinations thereof. Microporation is accomplished by (a) ablating the stratum corneum by localized rapid heating of water such that such water is vaporized, thus eroding the cells; (b) puncturing the stratum corneum with a micro-lancet calibrated to form a micropore of up to about 1000 .mu.m in diameter; (c) ablating the stratum corneum by focusing a tightly focused beam of sonic energy onto the stratum corneum; (d) hydraulically puncturing the stratum corneum with a high pressure jet of fluid to form a micropore of up to about 1000 .mu.m in diameter, or (e) puncturing the stratum corneum with short pulses of electricity to form a micropore of up to about 1000 .mu.m in diameter. A dye with an absorption maximum matched to the wavelength of a pulsed light source can be absorbed into the stratum corneum to concentrate the energy of the pulsed light source and aid in ablation of the stratum corneum. Alternatively, a hot wire can be caused to contact the stratum corneum.
摘要翻译：使用微孔和任选的声能和化学增强剂来描述增强皮肤对用于诊断目的的分析物的渗透性或用于治疗目的的药物的方法。如果选择，则可以通过频率调制，幅度调制，相位调制和/或其组合来调制声能。通过（a）通过局部快速加热水来消融角质层，使得这种水被蒸发，从而侵蚀细胞来实现微孔化; （b）用经过校准的微型刺血针刺穿角质层以形成直径约达1000微米的微孔; （c）通过将紧密聚焦的声能束聚焦在角质层上来消融角质层; （d）用高压喷射流体水力刺穿角质层以形成直径达约1000μm的微孔，或（e）以短脉冲电穿刺角质层以形成高达约直径1000亩。具有与脉冲光源的波长匹配的吸收最大值的染料可以被吸收到角质层中以集中脉冲光源的能量并有助于消除角质层。或者，可以使热丝接触角质层。

9. 发明授权

US07037277B1 System and method for fluid management in a continuous fluid collection and sensor device 失效
标题翻译：连续流体收集和传感器装置中流体管理的系统和方法
公开(公告)号：US07037277B1
公开(公告)日：2006-05-02
申请号：US09357452
申请日：1999-07-20
申请人： Alan Smith , Harry K. Delcher , Jonathan A. Eppstein , David Farquhar , Michael R. Hatch , Krishna Kumar
发明人： Alan Smith , Harry K. Delcher , Jonathan A. Eppstein , David Farquhar , Michael R. Hatch , Krishna Kumar
IPC分类号： A61B10/00
CPC分类号： A61B5/412 , A61B5/14514 , A61B5/14532 , A61B5/150022 , A61B5/150099 , A61B5/150221 , A61B5/150343 , A61B5/150755 , A61B5/15134 , A61B10/0045 , A61B2010/008 , A61B2017/00398 , A61B2017/00561
摘要： A fluid collection and sensor device for placement over at least one artificial opening made in a biological membrane for measuring a characteristic of a biological fluid collected from the tissue through the at least one artificial opening. The device comprises a sensor positioned in a flow path of the biological fluid for contacting a quantity of the biological fluid and generating an indication of a characteristic of the biological fluid. According to one aspect of the invention, a waste fluid storage element, such as a reservoir, is positioned in the device to collect the biological fluid after it has made contact with the sensor. According to another aspect of the invention, various surfaces of the fluid flow path of the fluid collection and sensor device are treated with an agent to limit or minimize clotting, aggregation or sepsis of the biological fluid, blockage or clogging of the flow path or degradation of the sensor. According to still another aspect of the invention, various configurations of a fluid sensor and collection device are provided that are designed to ensure that measurements are made on independent fluid samples.
摘要翻译：一种流体收集和传感器装置，用于放置在生物膜上制造的至少一个人造开口上，用于测量通过至少一个人造开口从组织收集的生物流体的特征。该装置包括位于生物流体的流动路径中的传感器，用于接触一定数量的生物流体并产生生物流体特征的指示。根据本发明的一个方面，诸如储存器的废液储存元件定位在装置中以在生物流体与传感器接触之后收集生物流体。根据本发明的另一方面，流体收集和传感器装置的流体流动路径的各个表面用试剂处理以限制或最小化生物流体的凝结，聚集或败血症，流动路径的堵塞或堵塞或降解的传感器。根据本发明的另一方面，提供了流体传感器和收集装置的各种构造，其被设计成确保对独立流体样品进行测量。

10. 发明授权

US07384396B2 System and method for continuous analyte monitoring 有权
标题翻译：用于连续分析物监测的系统和方法
公开(公告)号：US07384396B2
公开(公告)日：2008-06-10
申请号：US10435221
申请日：2003-05-08
申请人： Mark A. Samuels , Jonathan A. Eppstein , Michael R. Hatch , Alan Smith , Mark Faupel
发明人： Mark A. Samuels , Jonathan A. Eppstein , Michael R. Hatch , Alan Smith , Mark Faupel
IPC分类号： A61B5/00
CPC分类号： A61B5/14514 , A61B5/00 , A61B5/0002 , A61B5/14532 , A61B5/150022 , A61B5/150099 , A61B5/150809 , A61B5/150816 , A61B5/150824 , A61B5/150862 , A61B5/150969 , A61B5/150984 , A61B5/15134 , A61B5/155 , A61B5/157 , A61B10/0045 , A61B2010/008
摘要： A system and method for extracting a biological fluid from an organism and continuously monitoring its characteristics. The system includes a tissue interface device suitable for positioning on or about the surface of the biological membrane of the organism and a monitor and control unit coupled to the tissue interface device. The tissue interface device includes a sensor positioned in a flow path of the fluid for continuously sensing a characteristic of the biological fluid as it flows out from the one or more artificial openings formed in the biological membrane. The sensor generates a sensor signal representative thereof. The monitor and control unit electrically or optically reads the sensor to obtain a measurement of a characteristic, such as concentration of a particular analyte, of the biological fluid on a continuous basis.
摘要翻译：一种用于从生物体提取生物流体并连续监测其特征的系统和方法。该系统包括适于定位在生物体的生物膜的表面上或周围的组织界面装置以及耦合到组织界面装置的监测和控制单元。组织接口装置包括定位在流体的流动路径中的传感器，用于在生物流体从形成在生物膜中的一个或多个人造开口流出时持续感测生物流体的特性。传感器产生代表其的传感器信号。监视器和控制单元以电或光学方式读取传感器，以连续的方式获得生物流体特性的浓度，例如特定分析物的浓度。

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