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    Electroporation apparatus for control of temperature during the process
    1.
    发明授权
    Electroporation apparatus for control of temperature during the process 失效

    公开(公告)号：US6150148A

    公开(公告)日：2000-11-21

    申请号：US176136

    申请日：1998-10-21

    申请人： Gurvinder Singh Nanda ,  Rejean Laverdiere ,  Gunter A. Hofmann

    发明人： Gurvinder Singh Nanda ,  Rejean Laverdiere ,  Gunter A. Hofmann

    IPC分类号： C12M3/00 ,  C12N13/00

    CPC分类号： C12M35/02

    摘要： An electroporation method and apparatus generating and applying an electric field according to a user-specified pulsing and temperature profile scheme. The apparatus includes a cuvette holder with a Peltier device forming part of the electrode structures that form part of the holder. Advantageously, one such pulse includes a low voltage pulse of a first duration, immediately followed by a high voltage of a second duration, immediately followed by a low voltage of a third duration. The low voltage electroporation field accumulates molecules at the surface of a cell, the appropriately high voltage field creates an opening in the cell, and the final low voltage field moves the molecule into the cell. The molecules may be DNA, portions of DNA, chemical agents, the receiving cells may be eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, sperm, or other suitable cells. The molecules are placed in close proximity to the cells, either in the interstitial space in tissue surrounding the cells or in a fluid medium containing the cells.

    Intradermal delivery of active agents by needle-free injection and electroporation
    2.
    发明授权
    Intradermal delivery of active agents by needle-free injection and electroporation 有权
    通过无针注射和电穿孔活性剂的皮内递送

    公开(公告)号：US07171264B1

    公开(公告)日：2007-01-30

    申请号：US10339708

    申请日：2003-01-08

    申请人： Gunter A. Hofmann ,  Dietmar P. Rabussay ,  Lei Zhang

    发明人： Gunter A. Hofmann ,  Dietmar P. Rabussay ,  Lei Zhang

    IPC分类号： A61N1/30

    CPC分类号： A61N1/0424 ,  A61N1/0428 ,  A61N1/325

    摘要： Methods are proved for introducing a biologically active agent into cells of a subject by introducing the agent in a form suitable for electrotransport into a region of tissue of the subject using one or more needle-free injectors, and applying a pulsed electric field to the region of tissue, thereby causing electroporation of the region of tissue. The combination of needle-free injection and electroporation is sufficient to introduce the agent into cells in skin, muscle or mucosa. For example, the region of tissue can be contacted with two oppositely charged injectors, one acting as the donor electrode and one acting as the counter electrode, or a single injector and one or more electrodes can be used. In addition, needle-free injection may be used in combination with suitable non-invasive electrode configurations. The active agents delivered into cells using the invention method can be small molecules, polynucleotides, polypeptides, and the like.

    摘要翻译： 证明通过使用一种或多种无针注射器将适合于电转移到受试者组织区域的形式引入生物活性剂来引入生物活性剂的方法，以及向该区域施加脉冲电场 的组织，从而引起组织区域的电穿孔。 无针注射和电穿孔的组合足以将药剂引入皮肤，肌肉或粘膜中的细胞中。 例如，组织区域可以与两个相反电荷的注射器接触，一个充当施主电极，另一个充当对电极，或者可以使用单个注射器和一个或多个电极。 此外，无针注射可以与合适的非侵入性电极结构组合使用。 使用本发明方法递送到细胞中的活性剂可以是小分子，多核苷酸，多肽等。

    Flow-through electroporation system for ex vivo gene therapy
    3.
    发明授权
    Flow-through electroporation system for ex vivo gene therapy 失效
    用于离体基因治疗的流通电穿孔系统

    公开(公告)号：US06746441B1

    公开(公告)日：2004-06-08

    申请号：US09470567

    申请日：1999-12-22

    申请人： Gunter A. Hofmann ,  Dietmar Rabussay

    发明人： Gunter A. Hofmann ,  Dietmar Rabussay

    IPC分类号： A61M3100

    CPC分类号： A61N1/327 ,  A61N1/306 ,  A61N1/325 ,  C12M35/02

    摘要： A method and apparatus for introducing a preselected molecule into a living cell by contacting the cell with the preselected molecule and applying a multiple series of electrical pulses to the cell. The method can be utilized ex vivo. The multiple electrical pulses generate rotating electric fields which introduce transient pores in the living cell without killing the cell. The rotating electric fields are provided in a flow through chamber apparatus having more than two electrodes. A three-step pulse process, e.g. collection, electroporation, electrophoresis, is used to introduce the preselected molecule into the cell. A mechanical means of repositioning cells between successive pulses is also provided. The apparatus can also provide a means to pulse cells at different temperatures and then after pulsing, let the cells recover for a specified residence time at another temperature.

    摘要翻译： 一种通过使细胞与预选分子接触并向细胞施加多系列电脉冲将预选分子引入活细胞的方法和装置。 该方法可以离体使用。 多个电脉冲产生旋转电场，其在活细胞中引入瞬时孔而不杀死细胞。 旋转电场设置在具有多于两个电极的流通室装置中。 三步脉冲处理，例如 收集，电穿孔，电泳，用于将预选分子引入细胞。 还提供了在连续脉冲之间重新定位电池的机械装置。 该装置还可以提供在不同温度下脉冲细胞的手段，然后在脉冲之后，让细胞在另一个温度恢复指定的停留时间。

    Method of programming an array of needle electrodes for electroporation therapy of tissue
    4.
    发明授权
    Method of programming an array of needle electrodes for electroporation therapy of tissue 有权
    编织电极阵列的方法，用于组织的电穿孔治疗

    公开(公告)号：US06216034B1

    公开(公告)日：2001-04-10

    申请号：US09227417

    申请日：1999-01-08

    申请人： Gunter A. Hofmann ,  Sukhendu B. Dev ,  Steven C. Dimmer ,  Jeffrey I. Levatter ,  Gurvinder S. Nanda

    发明人： Gunter A. Hofmann ,  Sukhendu B. Dev ,  Steven C. Dimmer ,  Jeffrey I. Levatter ,  Gurvinder S. Nanda

    IPC分类号： A61N130

    CPC分类号： A61N1/327 ,  A61B2018/143 ,  A61N1/325

    摘要： A method and apparatus for in vivo electroporation therapy. Using electroporation therapy (EPT) as described in the invention, tumors treated by a combination of electroporation using the apparatus of the invention and a chemotherapeutic agent caused regression of tumors in vivo. In one embodiment, the invention provides a method of EPT utilizing low voltage and long pulse length for inducing cell death. One embodiment of the invention includes a system for clinical electroporation that includes a needle array electrode having a “keying” element that determines the set point of the therapy voltage pulse and/or selectable array switching patterns. A number of electrode applicator designs permit access to and treatment of a variety of tissue sites. Another embodiment provides a laparoscopic needle applicator that is preferably combined with an endoscope for minimally invasive EPT.

    摘要翻译： 一种用于体内电穿孔治疗的方法和装置。 使用本发明所述的电穿孔治疗（EPT），通过使用本发明的装置的电穿孔和化学治疗剂的组合治疗的肿瘤引起体内肿瘤消退。 在一个实施方案中，本发明提供了一种利用低电压和长脉冲长度诱导细胞死亡的EPT的方法。 本发明的一个实施例包括用于临床电穿孔的系统，其包括具有确定治疗电压脉冲和/或可选阵列切换模式的设定点的“键控”元件的针阵列电极。 许多电极施加器设计允许访问和处理各种组织部位。 另一实施例提供一种腹腔镜针施加器，其优选地与用于微创EPT的内窥镜组合。

    Electroporation employing user-configured pulsing scheme
    5.
    发明授权
    Electroporation employing user-configured pulsing scheme 失效
    采用用户配置的脉冲方案进行电穿孔

    公开(公告)号：US6096020A

    公开(公告)日：2000-08-01

    申请号：US126941

    申请日：1998-07-30

    申请人： Gunter A. Hofmann

    发明人： Gunter A. Hofmann

    IPC分类号： C12M1/00 ,  A61M37/00 ,  C12M1/42 ,  C12M3/00 ,  C12N15/87 ,  H03K3/45 ,  H03K3/57 ,  A61M31/00

    CPC分类号： H03K3/57 ,  C12M35/02 ,  C12N15/87

    摘要： An electroporation method and apparatus generating and applying an electric field according to a user-specified pulsing scheme. Advantageously, one such pulse includes a low voltage pulse of a first duration, immediately followed by a high voltage of a second duration, immediately followed by a low voltage of a third duration. The low voltage electroporation field accumulates molecules at the surface of a cell, the appropriately high voltage field creates an opening in the cell, and the final low voltage field moves the molecule into the cell. The molecules may be DNA, portions of DNA, chemical agents, the receiving cells may be eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, sperm, or other suitable cells. The molecules are placed in close proximity to the cells, either in the interstitial space in tissue surrounding the cells or in a fluid medium containing the cells.

    摘要翻译： 根据用户指定的脉冲方案产生和施加电场的电穿孔方法和装置。 有利地，一个这样的脉冲包括第一持续时间的低电压脉冲，紧接着是第二持续时间的高电压，紧接着是第三持续时间的低电压。 低电压电场在电池表面积聚分子，适当的高电压场在电池中产生开口，最终的低电压场将分子移动到电池中。 分子可以是DNA，DNA的一部分，化学试剂，接收细胞可以是蛋，血小板，人细胞，红细胞，哺乳动物细胞，植物原生质体，植物花粉，脂质体，细菌，真菌，酵母，精子或其他 合适的细胞。 将分子放置在细胞附近，或者在围绕细胞的组织的间质空间中或在含有细胞的流体培养基中。

    Flow-through electroporation system for ex vivo gene therapy
    6.
    发明授权
    Flow-through electroporation system for ex vivo gene therapy 失效
    用于离体基因治疗的流通电穿孔系统

    公开(公告)号：US6027488A

    公开(公告)日：2000-02-22

    申请号：US90471

    申请日：1998-06-03

    申请人： Gunter A. Hofmann ,  Dietmar Rabussay

    发明人： Gunter A. Hofmann ,  Dietmar Rabussay

    IPC分类号： C12N15/09 ,  A61K48/00 ,  A61N1/32 ,  C12M1/00 ,  A61M37/00 ,  A61M31/00 ,  C12N13/00

    CPC分类号： A61N1/327 ,  A61N1/325 ,  C12M35/02 ,  A61N1/306

    摘要： A method and apparatus for introducing a preselected molecule into a living cell by contacting the cell with the preselected molecule and applying a multiple series of electrical pulses to the cell. The method can be utilized ex vivo. The multiple electrical pulses generate rotating electric fields which introduce transient pores in the living cell without killing the cell. The rotating electric fields are provided in a flow through chamber apparatus having more than two electrodes. A three-step pulse process, e.g. collection, electroporation, electrophoresis, is used to introduce the preselected molecule into the cell. A mechanical means of repositioning cells between successive pulses is also provided. The apparatus can also provide a means to pulse cells at different temperatures and then after pulsing, let the cells recover for a specified residence time at another temperature.

    摘要翻译： 一种通过使细胞与预选分子接触并向细胞施加多系列电脉冲将预选分子引入活细胞的方法和装置。 该方法可以离体使用。 多个电脉冲产生旋转电场，其在活细胞中引入瞬时孔而不杀死细胞。 旋转电场设置在具有多于两个电极的流通室装置中。 三步脉冲处理，例如 收集，电穿孔，电泳，用于将预选分子引入细胞。 还提供了在连续脉冲之间重新定位电池的机械装置。 该装置还可以提供在不同温度下脉冲细胞的手段，然后在脉冲之后，让细胞在另一个温度恢复指定的停留时间。

    Electroporation system with voltage control feedback for clinical applications
    7.
    发明授权
    Electroporation system with voltage control feedback for clinical applications 失效
    具有电压控制反馈的电穿孔系统用于临床应用

    公开(公告)号：US5810762A

    公开(公告)日：1998-09-22

    申请号：US930168

    申请日：1997-10-08

    申请人： Gunter A. Hofmann

    发明人： Gunter A. Hofmann

    IPC分类号： A61N1/32 ,  A61N1/30

    CPC分类号： A61N1/327 ,  A61N1/325

    摘要： An electrode apparatus for the application of electroporation to a portion of the body of a patient, comprising a support member, a pair of electrodes adjustably mounted on the support member for movement toward and away from one another for positioning on opposite sides of a body portion to be electroporated, a sensing element for sensing a distance between the electrodes and generating a distance signal proportionate to the distance between the electrodes, and means responsive to said distance signal for applying pulses of high amplitude electric energy to the electrodes proportionate to the distance between the electrodes.

    摘要翻译： PCT No.PCT / US95 / 04384 Sec。 371日期1997年10月8日第 102（e）日期1997年10月8日PCT提交1995年4月10日PCT公布。 出版物WO96 / 32155 日期1996年10月17日一种用于将电穿孔施加到患者身体的一部分的电极装置，包括支撑构件，可调节地安装在支撑构件上的一对电极，用于朝向和远离彼此移动以便相对定位 要被电穿孔的身体部分的侧面;感测元件，用于感测电极之间的距离并产生与电极之间的距离成比例的距离信号;以及响应于所述距离信号的装置，用于向电极施加高振幅电能的脉冲 与电极之间的距离成比例。