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1. 发明申请

US20050287620A1 METHOD OF DETERMINING ANALYTE LEVEL USING SUBCUTANEOUS ELECTRODE 审中-公开
标题翻译：使用细胞电极测定分析物水平的方法
公开(公告)号：US20050287620A1
公开(公告)日：2005-12-29
申请号：US11109379
申请日：2005-04-19
申请人： Adam Heller , Michael Pishko
发明人： Adam Heller , Michael Pishko
IPC分类号： G01N27/327 , A61B5/145 , A61B5/1473 , A61B5/1486 , A61B5/1495 , C12M1/40 , C12Q1/00 , C12Q1/54
CPC分类号： C12Q1/54 , C12Q1/006 , Y10S435/817 , Y10S435/917 , Y10S435/962
摘要： A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably three or four-layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer is overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited (third layer). An outer (fourth) layer is biocompatible.
摘要翻译：描述了设计用于皮下体内电导率监测葡萄糖的小直径柔性电极。电极被设计成允许“一点”体内校准，即即使在血清或血液的其它电反应物质的存在下也能在零葡萄糖浓度下具有零输出电流。电极优选为三层或四层，其中层叠在聚酰胺绝缘金线的尖端上的凹槽内。第一葡萄糖浓度 - 电流转导层用电绝缘和葡萄糖通量限制层（第二层）涂覆，其上任选地沉积固定的干扰消除辣根过氧化物酶基膜（第三层）。外（第四）层是生物相容的。

2. 发明申请

US20100059373A1 Subcutaneous Glucose Electrode 审中-公开
公开(公告)号：US20100059373A1
公开(公告)日：2010-03-11
申请号：US12551504
申请日：2009-08-31
申请人： Adam Heller , Michael Pishko
发明人： Adam Heller , Michael Pishko
IPC分类号： C12Q1/00
CPC分类号： C12Q1/54 , C12Q1/006 , Y10S435/817 , Y10S435/917 , Y10S435/962
摘要： A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably three or four-layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer is overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited (third layer). An outer (fourth) layer is biocompatible.

3. 发明授权

US06234990B1 Ultrasound enhancement of transdermal transport 失效
标题翻译：超声增强透皮运输
公开(公告)号：US06234990B1
公开(公告)日：2001-05-22
申请号：US08885931
申请日：1997-06-30
申请人： Stephen Rowe , Joseph Kost , Samir S. Mitragotri , Michael Pishko , Matthew Davis
发明人： Stephen Rowe , Joseph Kost , Samir S. Mitragotri , Michael Pishko , Matthew Davis
IPC分类号： A61B1720
CPC分类号： A61B5/14514 , A61B5/150022 , A61B5/150083 , A61B5/150099 , A61B5/150137 , A61B5/150259 , A61B5/150389 , A61B5/150969 , A61B5/150984 , A61B5/15136 , A61M37/0092 , A61M2037/0007
摘要： Methods and devices for application of ultrasound to a small area of skin for enhancing transdermal transport. An ultrasound beam having a first focal diameter is channelled into a beam having a second, smaller diameter without substantial loss of energy. Higher energy ultrasound can be used while causing less pain. Alternatively, ultrasound energy is applied through a vibrating element positioned just contacting, above or extending into the skin. Use of the element facilitates extraction of analyte and may enhance drug delivery. A two step noninvasive method involves application of ultrasound to increase skin permeability and removal of ultrasound followed by transdermal transport that can be further enhanced using a physical enhancer.
摘要翻译：将超声应用于小面积皮肤以增强透皮运输的方法和装置。具有第一焦距的超声波束被引导到具有第二较小直径的光束中，而实质上没有能量损失。可以使用更高能量的超声波，同时减少疼痛。或者，通过刚刚接触皮肤上方或延伸到皮肤的振动元件施加超声能量。元素的使用有助于提取分析物，并且可以增强药物递送。两步非侵入性方法涉及应用超声波以增加皮肤渗透性和去除超声，然后进行透皮转运，其可以使用物理增强剂进一步增强。

4. 发明申请

US20080160632A1 Use of mesoscale self-assembly and recognition to effect delivery of sensing reagent for arrayed sensors 审中-公开
标题翻译：使用中尺度自组装和识别来实现阵列传感器传感试剂的传递
公开(公告)号：US20080160632A1
公开(公告)日：2008-07-03
申请号：US11981485
申请日：2007-10-31
申请人： C. Grant Willson , Michael Pishko , David M. Johnson , Ben Rathsack , Zachary Hogan
发明人： C. Grant Willson , Michael Pishko , David M. Johnson , Ben Rathsack , Zachary Hogan
IPC分类号： G01N21/62 , G01N33/00
CPC分类号： G01N21/6452 , G01N21/253 , G01N21/6454 , G01N2021/6482
摘要： A system and method for the detection of analytes in a fluid, in one embodiment, includes a light source, a sensor array, sensing elements, and a detector. More particularly, the system and method relate to discriminating mixtures of analytes in a fluid. The sensor array is formed from a supporting member into which a plurality of sensing elements may be formed. The sensing element may have a predefined shape. The sensing element may be configured to produce a signal when the sensing element interacts with the analyte. In one embodiment, the identity of the analyte may be determined by the detection of the signal and the shape of the sensing element. Using pattern recognition techniques, the analytes within a multi-analyte fluid may be characterized.
摘要翻译：在一个实施例中，用于检测流体中分析物的系统和方法包括光源，传感器阵列，感测元件和检测器。更具体地，该系统和方法涉及区分流体中分析物的混合物。传感器阵列由可以形成多个感测元件的支撑构件形成。感测元件可以具有预定形状。感测元件可以被配置为当感测元件与分析物相互作用时产生信号。在一个实施例中，可以通过检测信号和感测元件的形状来确定分析物的身份。使用模式识别技术，可以对多分析物流体中的分析物进行表征。

5. 发明申请

US20070105176A1 Method and apparatus for glucose monitoring 有权
标题翻译：用于葡萄糖监测的方法和装置
公开(公告)号：US20070105176A1
公开(公告)日：2007-05-10
申请号：US11529280
申请日：2006-09-28
申请人： Bennett Ibey , Vamsi Yadavalli , Rebecca Rounds , Hope Beier , Gerard Cote , Michael Pishko
发明人： Bennett Ibey , Vamsi Yadavalli , Rebecca Rounds , Hope Beier , Gerard Cote , Michael Pishko
IPC分类号： C12Q1/54 , C12M3/00
CPC分类号： C12Q1/54 , G01N33/53 , G01N33/54366
摘要： This disclosure relates to systems, devices, and methods of sensing an analyte. An implantable sensor may be contacted with a test sample under conditions that permit a binding protein and a ligand of the sensor to interact in an analyte-dependent manner to produce an analyte-dependent signal, and (b) detecting the analyte-dependent signal with a detector. A binding protein may reversibly bind an analyte and/or a ligand. A binding protein may have a higher binding affinity for an analyte than for a ligand. A binding protein and a ligand may each include a fluorophore, the absorption and/or emission properties of which may change in an analyte-dependent manner. A binding protein and/or a ligand may be bound to an active or inactive substrate. Some embodiments of systems, devices, and methods may be practiced in vitro, in situ, and/or in vivo. Systems and/or devices of the disclosure may be configured to be wearable.
摘要翻译：本公开涉及感测分析物的系统，装置和方法。在允许结合蛋白和传感器的配体以分析物依赖的方式相互作用以产生分析物相关信号的条件下，可植入传感器可以与测试样品接触，并且（b）用分析物依赖的信号检测检测器结合蛋白质可以可逆地结合分析物和/或配体。结合蛋白质可能对分析物具有比配体更高的结合亲和力。结合蛋白和配体可以各自包括荧光团，其吸收和/或发射性质可以以分析物依赖的方式改变。结合蛋白和/或配体可以与活性或非活性底物结合。系统，装置和方法的一些实施方案可以在体外，原位和/或体内实践。本公开的系统和/或设备可以被配置为可穿戴的。

6. 发明申请

US20070215491A1 Subcutaneous Glucose Electrode 有权
公开(公告)号：US20070215491A1
公开(公告)日：2007-09-20
申请号：US11695612
申请日：2007-04-03
申请人： Adam Heller , Michael Pishko
发明人： Adam Heller , Michael Pishko
IPC分类号： G01N27/26
CPC分类号： C12Q1/54 , C12Q1/006 , Y10S435/817 , Y10S435/917 , Y10S435/962
摘要： A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably three or four-layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer is overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited (third layer). An outer (fourth) layer is biocompatible.

7. 发明申请

US20060003398A1 Subcutaneous glucose electrode 失效
标题翻译：皮下葡萄糖电极
公开(公告)号：US20060003398A1
公开(公告)日：2006-01-05
申请号：US11182634
申请日：2005-07-15
申请人： Adam Heller , Michael Pishko
发明人： Adam Heller , Michael Pishko
IPC分类号： C12Q1/54 , C12M3/00
CPC分类号： C12Q1/54 , C12Q1/006 , Y10S435/817 , Y10S435/917 , Y10S435/962
摘要： A small diameter flexible electrode designed for subcutaneous in vivo amperometric monitoring of glucose is described. The electrode is designed to allow “one-point” in vivo calibration, i.e., to have zero output current at zero glucose concentration, even in the presence of other electroreactive species of serum or blood. The electrode is preferably layered, with the layers serially deposited within a recess upon the tip of a polyamide insulated gold wire. A first glucose concentration-to-current transducing layer can be overcoated with an electrically insulating and glucose flux limiting layer (second layer) on which, optionally, an immobilized interference-eliminating horseradish peroxidase based film is deposited. An outer layer is preferably biocompatible.
摘要翻译：描述了设计用于皮下体内电导率监测葡萄糖的小直径柔性电极。电极被设计成允许“一点”体内校准，即即使在血清或血液的其它电反应物质的存在下也能在零葡萄糖浓度下具有零输出电流。电极优选是层叠的，其中层被串联地沉积在聚酰胺绝缘金线的尖端上的凹部内。可以用电绝缘和葡萄糖通量限制层（第二层）涂覆第一葡萄糖浓度 - 电流转导层，其上任选地沉积固定的干扰消除辣根过氧化物酶膜。外层优选是生物相容的。

8. 发明授权

US06491657B2 Ultrasound enhancement of transdermal transport 失效
标题翻译：超声增强透皮运输
公开(公告)号：US06491657B2
公开(公告)日：2002-12-10
申请号：US09861924
申请日：2001-05-21
申请人： Stephen Rowe , Joseph Kost , Samir S. Mitragotri , Michael Pishko , Matthew Davis
发明人： Stephen Rowe , Joseph Kost , Samir S. Mitragotri , Michael Pishko , Matthew Davis
IPC分类号： A61B1720
CPC分类号： A61B5/14514 , A61B5/150022 , A61B5/150083 , A61B5/150099 , A61B5/150137 , A61B5/150259 , A61B5/150389 , A61B5/150969 , A61B5/150984 , A61B5/15136 , A61M37/0092 , A61M2037/0007
摘要： Methods and devices for application of ultrasound to a small area of skin for enhancing transdermal transport. An ultrasound beam having a first focal diameter is channelled into a beam having a second, smaller diameter without substantial loss of energy. Higher energy ultrasound can be used while causing less pain. Alternatively, ultrasound energy is applied through a vibrating element positioned just contacting, above or extending into the skin. Use of the element facilitates extraction of analyte and may enhance drug delivery. A two step noninvasive method involves application of ultrasound to increase skin permeability and removal of ultrasound followed by transdermal transport that can be further enhanced using a physical enhancer.
摘要翻译：将超声应用于小面积皮肤以增强透皮运输的方法和装置。具有第一焦距的超声波束被引导到具有第二较小直径的光束中，而实质上没有能量损失。可以使用更高能量的超声波，同时减少疼痛。或者，通过刚刚接触皮肤上方或延伸到皮肤的振动元件施加超声能量。元素的使用有助于提取分析物，并且可以增强药物递送。两步非侵入性方法涉及应用超声波以增加皮肤渗透性和去除超声，然后进行透皮转运，其可以使用物理增强剂进一步增强。

9. 发明授权

US5947921A Chemical and physical enhancers and ultrasound for transdermal drug delivery 失效
标题翻译：用于透皮给药的化学和物理增强剂和超声波
公开(公告)号：US5947921A
公开(公告)日：1999-09-07
申请号：US574377
申请日：1995-12-18
申请人： Mark E. Johnson , Samir S. Mitragotri , Daniel Blankschtein , Robert S. Langer , Michael Pishko , Joseph Kost
发明人： Mark E. Johnson , Samir S. Mitragotri , Daniel Blankschtein , Robert S. Langer , Michael Pishko , Joseph Kost
IPC分类号： A61K9/00 , A61K41/00 , A61M37/00 , A61N1/32 , A61B17/00
CPC分类号： A61B5/14514 , A61K41/0047 , A61K9/0009 , A61M37/0092 , A61N1/325 , A61N1/327 , A61M2037/0007
摘要： Transdermal transport of molecules during sonophoresis (delivery or extraction) can be further enhanced by providing chemical enhancers which increase the solubility of the compound to be transported and/or lipid bilayer solubility, and/or additional driving forces for transport, such as mechanical or osmotic pressure, magnetic fields, electroporation or iontophoresis. In a preferred embodiment the ultrasound is low frequency ultrasound which induces cavitation of the lipid layers of the stratum corneum (SC). This method provides higher drug transdermal fluxes, allows rapid control of transdermal fluxes, and allows drug delivery or analyte extraction at lower ultrasound intensities and other forces or concentrations than that required if each means of enhancing transport is used individually.
摘要翻译：可以通过提供增加待运输的化合物和/或脂质双层溶解度的溶解度的化学增强剂和/或用于运输的附加驱动力（例如机械或渗透）来进一步增强超声波输送（递送或提取）期间分子的透皮转运压力，磁场，电穿孔或离子电渗疗法。在优选实施例中，超声是低频超声，其引起角质层（SC）的脂质层的空化。该方法提供较高的药物透皮通量，允许快速控制经皮通量，并允许在较低的超声强度下进行药物递送或分析物提取，以及如果分别使用增强转运的每种手段所需的其他力或浓度。

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