CN1253485A - 一种电外科医疗设备 - Google Patents

一种电外科医疗设备 Download PDF

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CN1253485A
CN1253485A CN98804483A CN98804483A CN1253485A CN 1253485 A CN1253485 A CN 1253485A CN 98804483 A CN98804483 A CN 98804483A CN 98804483 A CN98804483 A CN 98804483A CN 1253485 A CN1253485 A CN 1253485A
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科林·查理斯·欧文·戈布尔
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Gyrus Medical Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206Generators therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/14Probes or electrodes therefor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00636Sensing and controlling the application of energy
    • A61B2018/0066Sensing and controlling the application of energy without feedback, i.e. open loop control
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B2018/00636Sensing and controlling the application of energy
    • A61B2018/00696Controlled or regulated parameters
    • A61B2018/0075Phase
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206Generators therefor
    • A61B2018/1226Generators therefor powered by a battery
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/04Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
    • A61B18/12Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
    • A61B18/1206Generators therefor
    • A61B2018/1246Generators therefor characterised by the output polarity
    • A61B2018/1253Generators therefor characterised by the output polarity monopolar

Abstract

在一种电外科医疗设备中,该设备对变化的负载阻抗敏感,尤其是对变化的负载电抗非常敏感,固定射频发生器具有一个由至少一个功率输出器件构成的输出级(Q1,Q2,TR2-TR4,C1,VC2,42),并与电源器件相连,一个带有负载-依赖共振条件的输出网络。为了补偿在负载电抗中的变化,输出网络具有一个动态可变电容器(VC2),其保持网络的调谐基本恒定。通过相位比较器和伺服器件(44)对电容器(VC2)进行改变,其中伺服器件(44)响应由于负载电抗变化而导致的输出级中的相差的变化。

Description

一种电外科医疗设备
本发明涉及一种带有可变阻抗负载的射频频率发生器,更具体的涉及一种电外科医疗设备,其具有安装有此种发生器的单极电极,而发生器的工作频率通常超过5MHz。
公知的电外科医疗系统包含手持部分,具有从手持部分突出出来的单个治疗电极的单电极部分,发生器部分和将发生器部分与手持部分相连的电缆。这样的系统通常用于各种的电外科医疗。通常将导电垫加到病人的身体上,并与发生器部分的返回端相连,从而形成电外科医疗电流的回路。此种结构的缺点在于,在返回垫的区域中的组织内的电外科医疗电流的定位,特别是在较高频率的情况下,由于发生器和手持部分之间的电缆所产生的反应成分的不可预见性,导致在电极产生不可预见的电压。
通过在申请人的国际申请No.PCT/GB96/02557中所描述的设备至少部分的克服了上述缺点,其揭示了一种电外科医疗设备,其包含手持部分,具有从手持部分突出出来的单治疗电极的单极电极部分,和手持部分内的射频发生器,发生器具有一个单引导射频输出连接线,该输出连接线与电极耦合。另外发生器与外部元件相隔离。特别是,例如,发生器与接地的元件或与返回垫无其他引导射频输出连接。通过在手持部分内设置发生器,可避免由于通过电缆提供射频-频率电流的结果所造成的不可预测的阻抗的变化。射频返回电流借助位于发生器周围的导电屏蔽通过杂散电容耦合在病人和发生器间通过。
发生器的工作频率最好是5MHz或更大。频率越高,由于增大的频率在回路所造成的电抗降低而导致所获得的电流电平越大。可通过手持部分内的电池对发生器供电。这样可将辐射干扰降低到最小。
在发生器周围导电屏蔽的存在会使杂散电容的变化降低到最小,其中的杂散电容是由于患者用不同的方式夹持所造成的。屏蔽最好与发生器相隔离,并形成管状的手持部分体,即以金属壳的形式,或由电绝缘材料构成手持部分体,所述的电绝缘材料被金属化以提供导电屏蔽。在金属化层位于手持部分体的外面上部或手持部分体自身为金属的情况下,最好用电绝缘的外层盖住外部的金属表面。通过提供屏蔽,可降低杂散电容的变化,这是因为相关的发生器导体和屏蔽之间的电容是恒定的,且屏蔽提供与病人容性耦合的具有恒定面积的导电体。
虽然屏蔽可降低杂散电容的变化,阻抗负载的变化会维持能量效率造成相当大的困难,其中变化的阻抗是由于在组织-电极接口处改变条件时所造成的负载的不可避免的变化所引起的。在较小的程度上,在防止由于瞬间的不匹配所造成的输出装置的断路过程中会存在困难。
考虑到这些困难,根据本发明的第一方面,所提供的射频发生器在变化的负载状态下可工作在基本固定的频率,发生器具有一个输出级,该输出级包含一个输出功率装置,发生器还与功率器件相连,输出网络包含治疗电极输出节点,其中输出网络具有依赖于负载的谐振状态,并包括一个可变电抗元件,该元件设置用于至少部分的补偿由于在负载阻抗中的变化所导致的输出网络失谐。根据本发明的另外一个方面,本发明提供一种射频发生器,其在负载变化的情况下能够工作在基本上固定的频率下,发生器的输出级包括一个谐振输出电路,其具有一个可变电抗元件(诸如可变电容器),被设置用于至少部分的补偿负载阻抗的变化。可以通过监测在输出级中的相位的变化和最好机械的驱动电容器,响应所检测到的负载阻抗变化自动的改变电容,从而以这样一种方式改变电容,即使得所检测到的相位差达到一个最佳值或在一个最佳的范围内。可变电容器最好与发生器的输出变压器(其可以是隔离变压器或自耦变压器)的次级绕组并联,形成部分并联调谐输出电路,通过负载的阻抗可以影响该电路的调谐。
在此情况下,负载电抗的变化可以得到补偿,从而将输出电抗电路的调谐保持尽可能的实际,从而给出最接近真实负载阻抗的输出装置或装置(典型的是一对诸如功率MOSFET的功率晶体管器件)。因此,很满意的结果是,发生器负载阻抗的变化在不改变工作频率的情况下被维持在较宽的范围内。
此自耦调谐效应可允许通过使用高-Q输出级用于发生器输出的高效耦合,在如上所述的自含电池电源的电外科医疗设备中,一个重要的要求是通过设备、用户和病人之间的高的耦合获得高效的工作。
表示负载电抗的用于控制可变电容器的相位信息可通过将输出相位与驱动信号的相位进行比较而获得,例如,提供到输出变压器的初级线圈的射频信号或提供到输出装置的基极或栅极连接的驱动信号。然后将所获得的相位差信号进行放大以提供一个极性的电容器驱动信号,从而当负载阻抗降低时,可变电容同样降低,这样在当可变电容器与输出阻抗(例如变压器次级线圈)并联的情况下,会将较大比例的电流提供到负载。
需注意的是,发生器的输出电路可包含一个输出耦合电容器(即与发生器输出线路串联),而可变电容器可构成该耦合电容器,因为其同时构成输出谐振电路的一部分。在此情况下,通过降低负载阻抗,在降低可变电容值的同时还会降低输出电流值。此耦合电容器被用于限制发生器输出装置或类似装置上的负载。
可变电容器自身还可包含平行电容片,和用于改变片之间的空间间隔的装置诸如压电激励器。此类装置的好处在于可以承受与电外科医疗治疗相关的高压且可快速的工作,典型的在10ms之内。根据所使用的压电激励器的性质,还可获得更快的响应时间。通常,将高介电常数的层安插在电容片之间。
本发明包含电外科医疗设备,该设备安装一个如上所述的设置在手持部分之内的发生器。该设备具有一个单极治疗电极,其从手持部分突出出来,而发生器的可变电抗元件最好位于或邻近电极进入手持部分的接口位置。
下面将参考附图对本发明的实例进行描述。
图1示出所用的电外科医疗设备的示意图;
图2为设备的纵向截面图;
图3为处于使用状态的设备的等效电路图;
图4为本发明的并构成图1和图2的部分发生器的简化电路图;
图5为相位比较器的电路图;及
图6为根据本发明的另外一个发生器的简化电路图。
参考图1,自-含式的电外科医疗设备包含一个细长的柱状的手持部分10,如图所示通过“铅笔-方式”将其握住。手持部分的一个端部10A呈锥形,成单治疗电极12形式的电极部分从该端轴向伸出,从而其可与病人的身体14接触。在锥形端部10A上设置启动开关16。手持部分体10可由片状的金属构成,并提供有由膜材料构成的绝缘盖。另外,可通过电绝缘塑料材料模制出手持部分体10,并使内表面或外表面金属化。如果金属化部分位于外表面上,可提供一个电绝缘覆层,以将金属化部分与用户的手进行隔离。
在图2的截面图中,所示出的手持部分体10包含导电罩10S和绝缘壳10C。包含射频发生器和电池的内部电子部分18被安装在罩10S内。虽然如图所示,通过罩10C将电子部分18完全的包裹上并不是非常重要,最好至少发生器部分落在罩的长度方向的范围内。罩10具有多种用途。内部电子部分18具有非一致的物质,并分布在壳内,相对地具有不同的电势。罩10C提供相同或均匀电势的表面。通过使绝缘层10I的尺寸和厚度最小,罩的尺寸可被制的最大,从而与病人、用户和外部接地物体的电容耦合可做到最大。
通过使罩成为环形连续的形状,内部电子元件可有效的屏蔽射频辐射的潜在的干扰。用金属制造壳的好处在于在提供罩功能的同时,还具有另外的好处,即罩可提供均匀的热扩散,因此可改善电子部分内由于无效的工作所造成的功率消耗。
参考图3,现在讨论在使用状态的设备的等效电路图。在手持部分体内,设置一个射频发生器18G,其工作在(在图3中未示出开关16和罩10S)工业、科学或医疗频带中的其中一个5MHz频率上。在最好的设备中,工作频率为40.65MHz。其他可能的频率包含6.79MHz,13.65MHz,27.1MHz和915MHz。发生器具有一个与电极12耦合的输出连接(图1),且不具有其他的将电流引导到病人的输出连接。发生器18G的导电元件(在图3中用标号20表示元件)充当天线22,并通过手持部分体10的导电罩10S(参考图1和图2)借助电容24与病人14间接容性耦合,在图3中作为第二天线。用线26表示电极与组织接口。因此,当在使用时,发生器18G的有源输出连接通过被操作的组织与病人14相连,在图3中用电阻28表示此组织的电阻。此电阻的典型值为1千欧姆,并可降低到100欧姆。
发生器18G的辐射导体20同样通过电容30与用户容性相连,其是发生器与罩和罩与用户的电容的串联组合,正如电容34所表示的,用户32轮流与低容性耦合,在用户和病人之间存在间接和直接的容性路径。类似的,存在一个从发生器导电元件20通过手持部分体10(特别是罩10S)电容38到地的间接路径和病人14与地之间的串联电容。发生器18G和病人14之间的总的电容至少是15pF,其分别来自发生器对病人的电容24、手持部分体对用户的电容30、用户对地的电容34、身体对地的电容38和病人对地的电容36。
在图中未示出电池,其同样被装在手持部分体10内。其最好是镍-镉或锂-离子电池,通过机体10的与电极12的相对的端子可进行充电。
该设备主要的但并不局限于精细的医疗工作,诸如椎骨、神经、整形外科、耳-鼻-喉即牙科的治疗,以及办公室的流程。
现在参考图4,设备的发生器包含在晶体管Q4基础上的固定频率晶体振荡器,建立在晶体管Q3基础上的驱动级并具有一个驱动变压器TR1,和建立在晶体管Q1和Q2基础上的推-挽输出级。晶体管Q1和Q2为MOSFET,且被连接在高压电源之间(通常为50V),并具有一个公共的输出连接40,由此通过耦合电容C5可向输出变压器TR2的初级绕组输送位于振荡频率的射频功率信号。变压器TR2的次级绕组通过耦合电容C1与发生器输出42耦合。可变电容器VC2充当调谐元件,与表示杂散电容的电容Cstray一起将电极和与其连接的导体接地。感应变压器TR3和TR4分别与变压器TR2的初级和次级绕组串联连接,其次级绕组供电给相比较器和伺服驱动电路44用于驱动可变电容器VC2。
可以看出,输出级具有两个谐振电路。串联电路包含电容器C5,TR2的漏感和TR3,串联电路还包含变压器(主元件)TR2的次级绕组,TR4的初级绕组,以及由可变电容VC2,耦合电容C1和杂散电容Cstray所构成的电容器阵列。这两个谐振电路之间的相互关系随着负载和杂散电容而发生变化。串联谐振电路基本上不受影响。当与输出42相连的并联电路受负载和杂散电容的影响。相应的,在电路与输出变压器TR2的初级绕组相关的情况下,通过使用变压器TR3和TR4从输出电路(与输出42相关)和输出电路的电路上游部分获取感应信号,可获得用于改变电容器VC2的电容的相差信号,从而补偿负载和杂散电容中的失谐变化。
此时应注意,需要指出任何固定值阻抗匹配电路表现出电感性或电容性,他们损害输出开关切换装置Q1,Q1的开关效率。这是因为,此种的阻抗变化伴随着相位的变化,可使用应用谐振电路降低谐波的输出级,以获得用于相位比较器44的相位感测信号。
在图5中详细示出了相位比较器,以及变压器TR3和TR4。如上所述,通过变压器TR3和TR4的次级绕组提供用于相位比较器的信号电平。从每个与变压器TR2相关的调谐电路提供相位信息。通过对接收并联相位信号的变压器使用分离的绕组,借助二极管D11,D12可产生交替周期的独立半波整流,通过将串联相位信号的相位进行混合,可校正相位比较器。然而,当两个感应信号彼此相对具有90度的相位偏差时,在半波整流器D11,D12的输出所产生的误差电压仅为零。如图5中所示,通过可变电容器RV1和C13的组合可提供预设的相位偏移,其中电容器C13与变压器TR4的次级绕组并联连接,一设定输出变压器TR2的初级和次级之间的最佳的相差(参见图4)。在图5中,通过电阻-电容R11,C11和R12,C12的组合可提供平滑的整流器输出电压,且通过一个比较器(未示出)对来自输出46的输出误差电压进行放大并加到适宜的驱动电路(同样未示出)。此驱动电路安装一个主极点,用于补偿在反馈环路中由于例如在与可变电容器VC2的组装相关的机械谐振中所产生的电势的不稳定。
现在参考图4,可变电容器VC2,耦合电容器C1和输出电容结构的杂散电容对输出谐振电路的调谐都起作用。通过使用可变电容元件作为调谐电容器,可获得最大的电流输送。特别是,通过设置比较器和驱动器,从而当负载阻抗降低时,输出变压器两端产生相应的相差变化,可变电容器VC2的电容降低,并可将较大部分的有效电流提供到负载。需注意的是,作为一种变化,可变电容可被代替作为输出耦合电容器C1。在此情况下,负载阻抗的降低会同时使可变耦合电容和有效电流降低,这在当切换器件Q1,Q2需要被保护防止过重负载时很有用。
可变电容器VC2具有不同的形式。其最好是由平行板电容器构成,通过压电陶瓷激励器控制片的分离程度。可通过两种不同的方式生产激励器:(a)以与双金属带类似的方式形成弯曲的带或(b)轴向的固体压电元件(其可为单层或多层)。此类的激励器通过美国Ohio,Bedford的Morgan Matroc,Inc公司可获得。
弯带型激励器对应变化的所施加的电压通过在两个结合材料之间产生不同的膨胀而产生机械运动。通过将压电陶瓷材料接合到金属基片上而形成弯曲。由于陶瓷可被极化压缩和膨胀,因此可在两个方向上产生运动。同样,可用压电材料覆到金属基片的两侧,从而在相反的方向上极化每个覆层,以增强运动的程度。当向带上施加电压时,产生弯曲。通常所施加的电压在50V到100V之间,此产生用于改变可变电容器的电容的足够的运动。通常可获得8到24pF的电容变化。
对于轴向压电激励器,直接使用压电运动。激励器由多层元件构成,以响应所施加的电压获得足够的运动。通常的,轴向压电激励器比弯曲带类具有更快的响应时间。
通过机电或电磁技术,例如通过使用移动的线圈器件同样可改变可边电容器VC2的电容。
电容器自身(图中未示出)包含平行板,插入薄的介电层,该层具有高的介电常数。最好的材料是云母,其可以薄的叠层形式获得。此种材料的介电强度在每毫米40到200kV之间。如上所述,由于电容器被用做调谐电路调谐电容器或功率耦合电容器,电容器片两端的电压可达到1kV。典型的,介电层的厚度范围为25微米到50微米。对于相对介电常数为6的介电层,可构成每平方毫米为2pF的平行板电容器。具有50微米的总偏差,因此最小的电容为0.16pF/平方毫米(mmsq)。
对于图1和图2中所示的手持部分内的可变电容器VC2的物理位置,最好将其固定在电极进入手持部分的接口的区域内,以便将发生器的输出42(图4)和露出的电极12之间的导线长度降低到最小。
当可变电容器VC和与其相关的控制电路的响应速度变快时,电外科医疗作用的实质在于,由于在负载阻抗中的快速变化会发生某些瞬时的不匹配(例如由于形成电弧和断裂)。为了将输出器件Q1,Q1上的瞬时电压效应将到最小,如图所示,在每个输出MOSFET Q1,Q2上设置反向偏压肖特基二极管D1,D2。以高速率变化的过压并联器件Q1、Q2被二极管D1,D2的导通的限制并不是很大,而主要是通过他们的变容二极管起作用。虽然这些二极管D1,D2增大了开关电容,通过驱动作为部分电感负载的输出级,可以对其进行补偿,从而输出器件上的净效应是纯电阻性的,在发生过大的不匹配时的情况除外。
图4中所示的发生器的输出级为轨-轨相连的图腾柱结构的C级输出级。图6中示出了另外一个输出级。在此情况下,分别建立在晶体管Q3和Q4基础上的晶体振荡器和驱动器的功能保持与钳位齐纳二极管D3到D6一样,其中钳位齐纳二极管D3到D6与输出器件Q11,Q12的栅极连接并联。然而,输出器件Q11,Q12被如图6中所示,和另外的肖特基二极管设置成半-桥结构,并将具有输出变压器TR5的初级线圈的输出器件串联在半桥结构之间。输出谐振电路与图4的实施例中的相同。
为了简化,在图6中未示出相位感测电路。然而,需注意的是,可使用图5的相位比较器,使其中一个输入变压器连接在用于输出器件的射频栅极驱动电路中,而另外一个与前面的一样与输出变压器TR1的次级绕组串联连接。
简而言之,上述的电路通过使用快速响应线性激励器和在输出谐振电路中通过可变电抗的相位比较提供快速的电容变化,所述的线性激励器工作在较小的移动范围内。响应于相位比较提供对可变电抗元件的驱动。

Claims (17)

1.一种能够在可变负载情况下工作在基本固定频率上的射频电外科医疗发生器,该发生器具有一个输出级,该输出级包含一个功率输出器件,输出网络包含治疗电极输出节点,其中输出网络具有依赖于负载的谐振状态,并包含一个可变电抗元件,该元件设置用于至少部分的补偿由于在负载阻抗中的变化所导致的输出网络失谐。
2.根据权利要求1所述的发生器,其特征在于可变电抗元件与功率器件和所述节点之间的信号路径相关。
3.根据权利要求1所述的发生器,其特征在于包含一个感测电路,其具有一个与可变电抗元件耦合的输出,其中感测电路被设置成以感测负载阻抗变化并在所述的输出中产生负载阻抗响应调节信号,其中电抗元件被设置成使得其可以响应调节信号调节其电抗,从而进行所述的补偿。
4.根据权利要求3所述的发生器,其特征在于感测电路可以感测负载电抗的变化。
5.根据权利要求3所述的发生器,其特征在于感测电路包含相位比较器,其具有与输出级的各个不同部分耦合设置的输入端,以在感测电路中产生输出一个调节信号,用于调节电抗器件,从而使相位比较器输入信号之间的相位差达到预定的值或位于预定的范围。
6.根据权利要求1所述的发生器,其特征在于可变电抗元件为可变电容器。
7.根据权利要求1所述的发生器,其特征在于可变电抗元件包含一个伺服器件。
8.根据权利要求1所述的发生器,其特征在于输出级包含一个输出变压器,而可变电抗元件与变压器的次级绕组耦合。
9.根据权利要求1所述的发生器,其特征在于可变电抗元件形成并行-调谐输出网络的一部分。
10.根据权利要求9所述的发生器,其特征在于可变电抗元件为电容器,而调谐电路包含一个变压器绕组。
11.根据权利要求1所述的发生器,其特征在于输出网络包括一个发生器输出线路,其中可变电抗元件与输出线路串联连接。
12.根据权利要求11所述的发生器,其特征在于可变电抗元件为电容器。
13.根据权利要求1所述的发生器,其特征在于可变电抗元件形成功率元件和发生器的输出节点之间的输出电路的一部分。
14.根据前面任一权利要求所述的发生器,其特征在于发生器具有一个作为天线的导电元件。
15.一种电外科医疗设备,其包含一个手持部分,一个从手持部分突出出来的治疗电极,和一个如前面任一权利要求所述的发生器,其具有与治疗电极相连的发生器治疗电极输出节点。
16.根据权利要求15所述的设备,其特征在于其具有一个单治疗电极。
17.根据权利要求16所述的设备,其特征在于发生器的结构使得在使用期间它的射频返回通道是由电磁场传输通过病人和设备之间的空气产生的。
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US6325799B1 (en) 2001-12-04
GB9708268D0 (en) 1997-06-18
AU7069098A (en) 1998-11-13
JP2001521431A (ja) 2001-11-06
CA2286835A1 (en) 1998-10-29
KR20010020243A (ko) 2001-03-15
WO1998047436A1 (en) 1998-10-29

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