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51. 发明申请

US20050282284A1 Controlled electroporation and mass transfer across cell membranes in tissue 有权
标题翻译：控制电穿孔和组织中细胞膜的传质
公开(公告)号：US20050282284A1
公开(公告)日：2005-12-22
申请号：US11139012
申请日：2005-05-26
申请人： Boris Rubinsky , Yong Huang
发明人： Boris Rubinsky , Yong Huang
IPC分类号： C12N15/87
CPC分类号： A61N1/327 , A61N1/0412 , A61N1/0476 , A61N1/3754 , C12M35/02 , C12N15/87
摘要： Electroporation is performed in a controlled manner in individual and multiple biological cells present in biological tissue by monitoring the electrical impedance, defined herein as the ratio of current to voltage in the electroporation cell. The impedance detects the onset of electroporation in the biological cell(s), and this information is used to control the intensity and duration of the voltage to assure that electroporation has occurred without destroying the cell(s). This is applicable to electroporation in general.
摘要翻译：通过监测电气阻抗（在本文定义为电穿孔细胞中的电流与电压的比率），以受控的方式在存在于生物组织中的个体和多个生物细胞中进行电穿孔。阻抗检测生物细胞中电穿孔的发生，并且该信息用于控制电压的强度和持续时间，以确保电穿孔已经发生而不破坏细胞。这适用于一般的电穿孔。

52. 发明授权

US06562604B2 Controlled electroporation and mass transfer across cell membranes 有权
公开(公告)号：US06562604B2
公开(公告)日：2003-05-13
申请号：US09863117
申请日：2001-05-22
申请人： Boris Rubinsky , Yong Huang
发明人： Boris Rubinsky , Yong Huang
IPC分类号： C12N1300
CPC分类号： G01N33/48728 , C12M35/02 , C12N15/87
摘要： Electroporation is performed in a controlled manner in either individual or multiple biological cells or biological tissue by monitoring the electrical impedance, defined herein as the ratio of current to voltage in the electroporation cell. The impedance detects the onset of electroporation in the biological cell(s), and this information is used to control the intensity and duration of the voltage to assure that electroporation has occurred without destroying the cell(s). This is applicable to electroporation in general. In addition, a particular method and apparatus are disclosed in which electroporation and/or mass transfer across a cell membrane are accomplished by securing a cell across an opening in a barrier between two chambers such that the cell closes the opening. The barrier is either electrically insulating, impermeable to the solute, or both, depending on whether pore formation, diffusive transport of the solute across the membrane, or both are sought. Electroporation is achieved by applying a voltage between the two chambers, and diffusive transport is achieved either by a difference in solute concentration between the liquids surrounding the cell and the cell interior or by a differential in concentration between the two chambers themselves. Electric current and diffusive transport are restricted to a flow path that passes through the opening.

53. 发明授权

US6041787A Use of cryoprotective agent compounds during cryosurgery 失效
标题翻译：在冷冻手术中使用冷冻保护剂
公开(公告)号：US6041787A
公开(公告)日：2000-03-28
申请号：US42834
申请日：1998-03-17
申请人： Boris Rubinsky
发明人： Boris Rubinsky
IPC分类号： A01N1/02 , A61B17/00 , A61B18/00 , A61B18/02 , A61B19/00 , A61B17/36
CPC分类号： A01N1/02 , A01N1/0221 , A61B18/02 , A61B2017/00274 , A61B2018/00547 , A61B2018/0262 , A61B2018/0275 , A61B2090/0463 , A61B2090/374 , A61B2090/378 , A61B2218/002
摘要： The invention features an apparatus and method for protecting tissue from freeze damage during cryosurgery. According to the method, a cryoprotective agent is introduced to a tissue to be protected in an amount sufficient to protect the tissue from damage during cryosurgery, and cryosurgery is performed on tissue to be destroyed.
摘要翻译：本发明的特征在于一种用于在冷冻手术期间保护组织不受冻伤的装置和方法。根据该方法，将冷冻保护剂引入待保护的组织中，其量足以保护组织免于冷冻手术中的损伤，并对要破坏的组织进行冷冻手术。

54. 发明授权

US5746210A Device and method for detection, localization, and characterization of inhomogeneities in turbid media 失效
公开(公告)号：US5746210A
公开(公告)日：1998-05-05
申请号：US24278
申请日：1993-02-26
申请人： David A. Benaron , Boris Rubinsky
发明人： David A. Benaron , Boris Rubinsky
IPC分类号： A61B5/00 , A61B17/00 , A61B17/068 , A61B18/00 , A61B18/14 , G01N21/47 , A61B6/00
CPC分类号： A61B5/6848 , A61B18/00 , A61B5/0075 , A61B5/0084 , A61B5/14553 , G01N21/4795 , A61B17/068 , A61B18/14 , A61B2017/00022 , A61B2017/00123 , A61B2017/00508 , A61B2017/00557 , A61B2560/0276 , A61B2562/0242 , A61B2562/08 , A61B5/0073
摘要： The present invention provides a detection or imaging device and method that measures an effect upon the path traveled by a radiative wave through a medium where scattering of the radiative wave is strong, and uses this measured path effect to detect, localize, or characterize inhomogeneities in the medium, as well as of the medium itself, over time or space. In this embodiment, a radiative source (43), temporally modulated or intensity quantitated, is emitted into the medium (47). A detector (48) records radiative effects detected after travel through said medium, and the detected signal is measured for a path effect (45). Based upon one or more of these path effects, such as the distance the latest arriving photons have traveled, a quantifiable parameter of the medium is determined (49). This parameter can be the location, distance, speed, or other characteristic of the medium or inhomogeneity. Measurement over space provides additional information as to spatial distribution; measurement over time provides information as to temporal changes in the medium. The device has application in medical and industrial imaging, detection, and localization of objects and other inhomogeneities, as well as characterization of the medium itself, in media which highly scatters radiative waves emitted into the medium.

55. 发明授权

US5706810A Magnetic resonance imaging assisted cryosurgery 失效
标题翻译：磁共振成像辅助冷冻手术
公开(公告)号：US5706810A
公开(公告)日：1998-01-13
申请号：US461253
申请日：1995-06-02
申请人： Boris Rubinsky , John Gilbert , San Wong , Mark Roos , Grant Pease
发明人： Boris Rubinsky , John Gilbert , San Wong , Mark Roos , Grant Pease
IPC分类号： A61B18/02 , A61B19/00 , G01R33/28 , G01R33/561 , A61B5/055
CPC分类号： A61B18/02 , G01R33/28 , A61B2018/0262 , A61B2090/374 , A61B90/10 , G01R33/56308
摘要： Methods and apparatus for magnetic resonance imaging (MRI) assisted cryosurgery. Optimal probe placements and cooling parameters are calculated prior to cryosurgery using MRI data. A MRI compatible cryoprobe and a stereotactic probe positioning device are provided. The resolution of MR images is enhanced by mounting a radio frequency MR coil on the intracorporeal end of a cryoprobe. During cryosurgery the temperature distribution in the frozen region is solved by determining the boundary of the frozen region and solving the heat equation for the known boundary conditions. During cryosurgery the temperature distribution in the unfrozen region is determined by T1 measurements. The process of freezing is controlled using information from the solution of the energy equation in the frozen region and temperature measurements in the unfrozen region. After cryosurgery the extent of the tissue damage may be ascertained using phosphorus-31 and/or sodium-23 spectroscopy with a special coil set on the cryosurgical probe.
摘要翻译：磁共振成像（MRI）辅助冷冻手术的方法和装置。在使用MRI数据进行冷冻手术之前计算最佳探针放置和冷却参数。提供MRI兼容的冷冻探针和立体定向探针定位装置。通过将射频MR线圈安装在冷冻探针的体内末端来增强MR图像的分辨率。在冷冻手术中，通过确定冻结区域的边界并求解已知边界条件的热方程来解决冻结区域的温度分布。在冷冻手术中，未冻结区域的温度分布由T1测量确定。使用来自冻结区域的能量方程的解和来自未冻结区域的温度测量的信息来控制冷冻过程。在冷冻手术之后，可以使用在冷冻手术探针上设置的特殊线圈的磷-31和/或钠-23光谱来确定组织损伤的程度。

56. 发明授权

US4531373A Directional solidification for the controlled freezing of biomaterials 失效
标题翻译：用于生物材料受控冷冻的定向凝固
公开(公告)号：US4531373A
公开(公告)日：1985-07-30
申请号：US664164
申请日：1984-10-24
申请人： Boris Rubinsky
发明人： Boris Rubinsky
IPC分类号： A01N1/02 , F25D13/06 , F26B5/06 , G01N1/42
CPC分类号： G01N1/42 , A01N1/02 , A01N1/0257 , F25D13/062 , F26B5/06
摘要： Controlled freezing of a material (12) is accomplished by positioning an aliquot of the material (12) upon one surface (26) of a longitudinally extending substrate (14). First (30) and second (36) bases are provided each having heat transfer surfaces (32,40) which are adapted to sit in heat transfer relation with the other surface (24) of the substrate (14). The temperature of the first base (30) is controlled to be above the freezing temperature of the material (12). The temperature of the second base (36) is controlled to be below the freezing temperature of the material (12). The substrate (14) is moved longitudinally across the first base (30) in the direction of second base (36) while maintaining heat transfer relation of both bases (30,36) with the first surface (24) of the substrate (14). The frezzing rate of the material (12) is closely controlled and frozen material (12) can be produced in a continuous process.
摘要翻译：通过将材料（12）的等分试样定位在纵向延伸的基底（14）的一个表面（26）上来实现材料（12）的受控冷冻。提供第一（30）和第二（36）基座，每个基座具有适于与衬底（14）的另一表面（24）保持热传递关系的传热表面（32,40）。第一基座（30）的温度被控制为高于材料（12）的冷冻温度。将第二基座（36）的温度控制在材料（12）的冷冻温度以下。基板（14）沿着第二基座（36）的方向纵向移动穿过第一基座（30），同时保持两个基座（30,36）与基板（14）的第一表面（24）的热传递关系，。材料（12）的高效率被严格控制，冷冻材料（12）可以连续生产。

57. 发明授权

US09005189B2 Tissue ablation with irreversible electroporation 有权
标题翻译：组织消融与不可逆电穿孔
公开(公告)号：US09005189B2
公开(公告)日：2015-04-14
申请号：US13546339
申请日：2012-07-11
申请人： Rafael Davalos , Boris Rubinsky
发明人： Rafael Davalos , Boris Rubinsky
IPC分类号： A61B18/18 , A61B18/12 , A61N1/04 , A61B18/14 , A61N1/05 , A61N1/32
CPC分类号： A61B18/12 , A61B18/1233 , A61B18/1477 , A61B2018/00577 , A61B2018/00613 , A61B2018/1425 , A61N1/0412 , A61N1/0472 , A61N1/05 , A61N1/327
摘要： A new method for the ablation of undesirable tissue such as cells of a cancerous or non-cancerous tumor is disclosed. It involves the placement of electrodes into or near the vicinity of the undesirable tissue through the application of electrical pulses causing irreversible electroporation of the cells throughout the entire area of the undesirable tissue. The electric pulses irreversibly permeate the cell membranes, thereby invoking cell death. The irreversibly permeabilized cells are left in situ and are removed by the body immune system. The amount of tissue ablation achievable through the use of irreversible electroporation without inducing thermal damage is considerable.
摘要翻译：公开了一种用于消除不想要的组织的新方法，例如癌性或非癌性肿瘤的细胞。它涉及通过施加电脉冲将电极放置在不期望的组织附近或附近，从而在不期望的组织的整个区域内引起细胞的不可逆电穿孔。电脉冲不可逆地渗透细胞膜，从而引起细胞死亡。不可逆透化的细胞留在原位，并通过身体免疫系统去除。通过使用不可逆电穿孔而不引起热损伤可实现的组织消融量是相当大的。

58. 发明授权

US08835166B2 Extracellular matrix material created using non-thermal irreversible electroporation 有权
标题翻译：使用非热不可逆电穿孔产生细胞外基质材料
公开(公告)号：US08835166B2
公开(公告)日：2014-09-16
申请号：US13391577
申请日：2010-09-02
申请人： Mary Phillips , Elad Maor , Boris Rubinsky , Jacob Lavee
发明人： Mary Phillips , Elad Maor , Boris Rubinsky , Jacob Lavee
IPC分类号： A61B18/18 , A61L2/03 , A61L27/38 , A61K35/44 , A61K35/38 , A61K35/42 , A61K35/22 , A61K35/34 , A61L27/36
CPC分类号： A61K35/34 , A61K35/22 , A61K35/38 , A61K35/42 , A61K35/44 , A61L27/3604 , A61L27/3683 , A61L27/3834 , A61L2430/40
摘要： Extracellular matrix material is disclosed which is created by subjecting a target area to non-thermal irreversible electroporation (NTIRE) with a pulsed electrical field to kill cells in the absence of thermal damage. The dead cellular material may be removed and the remaining non-cellular matrix material may be implanted into a repair site to be treated medically or cosmetically.
摘要翻译：公开了细胞外基质材料，其通过用脉冲电场对目标区域进行非热不可逆电穿孔（NTIRE）而产生，以在不存在热损伤的情况下杀死细胞。可以去除死细胞材料，并将剩余的非细胞基质材料植入修复部位以进行医疗或化妆品处理。

59. 发明授权

US08298222B2 Electroporation to deliver chemotherapeutics and enhance tumor regression 有权
标题翻译：电穿孔提供化学治疗和增强肿瘤消退
公开(公告)号：US08298222B2
公开(公告)日：2012-10-30
申请号：US12430336
申请日：2009-04-27
申请人： Boris Rubinsky , Jon Edd , Liana Horowitz
发明人： Boris Rubinsky , Jon Edd , Liana Horowitz
IPC分类号： A61B18/10
CPC分类号： A61N1/327 , A61B18/1477 , A61B2018/1425 , A61N1/0412 , A61N1/0472
摘要： A method is disclosed for disrupting capillary blood flow and trapping materials such as chemotherapeutic agents in undesirable tissue, including cells of a cancerous or non-cancerous tumor. The method involves the placement of electrodes into or near the vicinity of capillary vessels supplying blood to capillaries in the undesirable tissue, and application of electrical pulses causing capillary blood flow disruption. In some cases, the electric pulses irreversibly permeate the cell membranes, thereby invoking cell death. The irreversibly permeabilized cells are left in situ and are removed by the body's immune system. The process may further comprise monitoring blood flow and/or infusion of a material such as a chemotherapeutic agent or marker into the blood.
摘要翻译：公开了一种用于破坏毛细血管血流并将诸如化学治疗剂的材料捕获在不期望的组织中的方法，包括癌性或非癌性肿瘤的细胞。该方法包括将电极放置在向不想要的组织中的毛细血管供应血液的毛细血管附近或附近，以及施加引起毛细血管血流破裂的电脉冲。在某些情况下，电脉冲不可逆地渗透细胞膜，从而引起细胞死亡。不可逆透化的细胞留在原位，并被身体的免疫系统除去。该方法还可以包括监测血液流动和/或将诸如化学治疗剂或标记物的材料输注到血液中。

60. 发明申请

US20120071874A1 TISSUE ABLATION WITH IRREVERSIBLE ELECTROPORATION 有权
公开(公告)号：US20120071874A1
公开(公告)日：2012-03-22
申请号：US13237199
申请日：2011-09-20
申请人： Rafael Davalos , Boris Rubinsky
发明人： Rafael Davalos , Boris Rubinsky
IPC分类号： A61B18/14
CPC分类号： A61B18/12 , A61B18/1233 , A61B18/1477 , A61B2018/00577 , A61B2018/00613 , A61B2018/1425 , A61N1/0412 , A61N1/0472 , A61N1/05 , A61N1/327
摘要： A new method for the ablation of undesirable tissue such as cells of a cancerous or non-cancerous tumor is disclosed. It involves the placement of electrodes into or near the vicinity of the undesirable tissue through the application of electrical pulses causing irreversible electroporation of the cells throughout the entire area of the undesirable tissue. The electric pulses irreversibly permeate the cell membranes, thereby invoking cell death. The irreversibly permeabilized cells are left in situ and are removed by the body immune system. The amount of tissue ablation achievable through the use of irreversible electroporation without inducing thermal damage is considerable.

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