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公开(公告)号：US06916656B2
公开(公告)日：2005-07-12
申请号：US10487235
申请日：2002-04-05
CPC分类号： C12M35/02 , A61K2039/5152 , A61K2039/5154 , C12N5/16 , C12N13/00 , H01L2224/83856 , H01L2924/01019
摘要： An object of the invention is to provide a method of treating biological cells prior to subjecting the biological cells to cell fusion pulses which includes the step of treating the biological cells with pre-fusion electric field waveforms which change amplitude in a non-linear way with respect to time, such that the biological cells are first aligned with a relatively low amplitude, long duration pre-fusion electric field waveform and then compressed with a relatively high amplitude, short duration pre-fusion electric field waveform resulting in increased cell membrane contact prior to being subjected to cell fusion. The non-linear pre-fusion electric field waveforms can change in a stepped way, in a continuous way, in a sigmoidal way, with step-wise increasing waveforms in adjacent steps, with step-wise increasing waveforms in non-adjacent steps, and in accordance with non-linear algorithms.
摘要翻译： 本发明的一个目的是提供一种在使生物细胞经历细胞融合脉冲之前处理生物细胞的方法，其包括用以非线性方式改变幅度的融合前电场波形来处理生物细胞的步骤， 相对于时间，使得生物细胞首先用相对低幅度，长持续时间的预融合电场波形对准，然后用相对较高幅度，短持续时间的预融合电场波形压缩，导致增加的细胞膜接触先 进行细胞融合。 非线性预融合电场波形可以以连续的方式以S形方式以相邻步骤中逐步增加的波形以逐步增加的波形在非相邻步骤中逐步增加，并以 按照非线性算法。
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2.发明申请METHOD AND APPARATUS FOR THE DELIVERY OF POLYNUCLEOTIDE CANCER VACCINES TO MAMMALIAN SKIN 审中-公开将多核苷酸疫苗递送给妈妈皮肤的方法和装置公开(公告)号：US20130123744A1
公开(公告)日：2013-05-16
申请号：US13138722
申请日：2010-03-26
申请人： Derin C. Walters , Alan D. King , Anna-Karin Maltais (formerly Anna-Karin Roos) , Britta Wahren , Kristian Haller (formerly Kristian Hallermalm) , Andreas Brave , Robert J. Walters
发明人： Richard E. Walters , Derin C. Walters , Alan D. King , Anna-Karin Maltais (formerly Anna-Karin Roos) , Britta Wahren , Kristian Haller (formerly Kristian Hallermalm) , Andreas Brave
IPC分类号： A61N1/30
CPC分类号： A61N1/306 , A61K39/00 , A61K39/0011 , A61K2039/53 , A61K2039/54 , A61N1/327 , C12N2770/24134
摘要： The invention provides a method and apparatus for the delivery of polynucleotide cancer vaccines to increase T cell response and reduce pain due to long electric waveform application and muscle contractions. The method includes the steps of: (a.) administering a polynucleotide cancer vaccine into the skin at an administration site, (b.) applying a needle electrode to the skin in the vicinity of the administration site, and (c.) applying a sequence of at least three electrical waveforms to deliver the polynucleotide cancer vaccine into skin cells by electroporation. The sequence has at least one of the following characteristics {1} at least two of the waveforms differ in amplitude, {2} at least two of the waveforms differ in width, and (3) a first waveform interval for a first set of two of the waveforms is different from a second waveform interval for a second set of two of the waveforms.
摘要翻译： 本发明提供了用于递送多核苷酸癌症疫苗以增加T细胞应答并减少由于长的电波形应用和肌肉收缩引起的疼痛的方法和装置。 该方法包括以下步骤：（a）在给药部位向皮肤施用多核苷酸癌症疫苗，（b）在给药部位附近向皮肤施用针电极，（c） 至少三个电波形的序列，以通过电穿孔将多核苷酸癌症疫苗递送到皮肤细胞中。 该序列具有以下特征中的至少一个{1}，至少两个波形幅度不同，{2}至少两个波形的宽度不同，（3）第一组二分之一的第一波形间隔 的波形与第二组波形的第二波形间隔不同。
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3.发明申请Method and apparatus for the delivery of polynucleotide vaccines to mammalian skin 审中-公开用于将哺乳动物皮肤递送多核苷酸疫苗的方法和装置公开(公告)号：US20110166501A1
公开(公告)日：2011-07-07
申请号：US13065135
申请日：2011-03-15
IPC分类号： A61M37/00
CPC分类号： A61N1/327 , A61K39/12 , A61K2039/53 , A61K2039/54 , A61K2039/70 , A61N1/306 , C07K14/005 , C12N2770/24122 , C12N2770/24134
摘要： An object of the invention is to provide a method and apparatus for the delivery of polynucleotide vaccines into mammalian skin cells to increase T cell response and to reduce pain and discomfort due to long electric waveform application and due to muscle contractions. The method for the delivery of polynucleotide vaccines into mammalian skin cells includes the steps of: (a.) administering a polynucleotide vaccine into the skin at an administration site, (b.) applying a needle electrode to the skin in the vicinity to the administration site, and (c.) applying a sequence of at least three single, operator-controlled, independently programmed, narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, to deliver the polynucleotide vaccine into the skin cells by electroporation. The sequence of at least three waveforms has one, two, or three of the following characteristics (1) at least two of the at least three waveforms differ from each other in waveform amplitude, (2) at least two of the at least three waveforms differ from each other in waveform width, and (3) a first waveform interval for a first set of two of the at least three waveforms is different from a second waveform interval for a second set of two of the at least three waveforms.
摘要翻译： 本发明的目的是提供一种用于将多核苷酸疫苗递送到哺乳动物皮肤细胞中以增加T细胞应答并减少由于长电波形应用引起的疼痛和不适以及由于肌肉收缩引起的疼痛和不适的方法和装置。 用于将多核苷酸疫苗递送到哺乳动物皮肤细胞中的方法包括以下步骤：（a）在给药部位将多核苷酸疫苗施用于皮肤，（b）将针电极施用于给药的附近的皮肤 站点，以及（c）应用脉冲间隔小于100毫秒的至少三个单个，操作者控制的，独立编程的窄间隔电波形序列，以通过电穿孔将多核苷酸疫苗递送到皮肤细胞中 。 至少三个波形的序列具有以下特征（1）中的一个，两个或三个，所述至少三个波形中的至少两个波形在波形幅度上彼此不同，（2）至少三个波形中的至少两个波形 在波形宽度上彼此不同，以及（3）至少三个波形中的两个的第一组的第一波形间隔与用于至少三个波形中的两个的第二组的第二波形间隔不同。
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4.发明申请METHOD AND APPARATUS FOR THE DELIVERY OF PLYNUCLEOTIDE VACCINES TO MAMMALIA SKIN 审中-公开将灭草鼠疫苗递送给妈妈皮肤的方法和装置公开(公告)号：US20110282265A1
公开(公告)日：2011-11-17
申请号：US12451536
申请日：2008-05-20
IPC分类号： A61M37/00
CPC分类号： A61N1/327 , A61K39/12 , A61K2039/53 , A61K2039/54 , A61K2039/70 , A61N1/306 , C07K14/005 , C12N2770/24122 , C12N2770/24134
摘要： An object of the invention is to provide a method and apparatus for the delivery of polynucleotide vaccines into mammalian skin cells to increase T cell response and reduce pain and discomfort due to long electric waveform application and due to muscle contractions. The method includes administering a polynucleotide vaccine into the skin at an administration site, (b) applying a needle electrode to the skin in the vicinity to the administration site, and (c) applying a sequence of at least three single, operator-controlled, independently programmed, narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, to deliver the 15 polynucleotide vaccine into the skin cells by electroporation.
摘要翻译： 本发明的目的是提供一种用于将多核苷酸疫苗递送到哺乳动物皮肤细胞中以增加T细胞应答并减少由于长电波形应用引起的疼痛和不适以及由于肌肉收缩而引起的不适的方法和装置。 该方法包括在给药部位向皮肤施用多核苷酸疫苗，（b）将针电极施用于给药部位附近的皮肤，以及（c）施用至少三个单独的，操作者控制的， 具有脉冲间隔小于100毫秒的独立编程的窄间隔电波形，以通过电穿孔将15个多核苷酸疫苗递送到皮肤细胞中。
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公开(公告)号：US07689641B2
公开(公告)日：2010-03-30
申请号：US10610833
申请日：2003-06-30
IPC分类号： G06F7/52
CPC分类号： G06F9/30014 , G06F5/01 , G06F7/49947 , G06F7/5338 , G06F9/30036 , G06F9/3885 , G06F2207/382 , G06F2207/3828
摘要： Method, apparatus, and program means for performing a packed multiply high with round and shift operation. The method of one embodiment comprises receiving a first operand having a first set of L data elements. A second operand having a second set of L data elements is received. L pairs of data elements are multiplied together to generate a set of L products. Each of the L pairs includes a first data element from the first set of L data element and a second data element from a corresponding data element position of the second set of L data elements. Each of the L products are rounded to generate L rounded values. Each of said L rounded values are scaled to generate L scaled values. Each of the L scaled values are truncated for storage at a destination. Each truncated value is to be stored at a data element position corresponding to its pair of data elements.
摘要翻译： 方法，装置和程序装置，用于执行具有循环和换档操作的压缩倍增。 一个实施例的方法包括接收具有第一组L个数据元素的第一操作数。 接收具有第二组L个数据元素的第二操作数。 将L对数据元素相乘以生成一组L个乘积。 L对中的每一个包括来自第一组L数据元素的第一数据元素和来自第二组L个数据元素的相应数据元素位置的第二数据元素。 每个L产品都被舍入，以产生L个舍入值。 每个所述L舍入值被缩放以产生L个缩放值。 L缩放值中的每一个都被截断以存储在目的地。 每个截断的值被存储在与其对数据元素对应的数据元素位置处。
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6.发明授权公开(公告)号：US06653114B2
公开(公告)日：2003-11-25
申请号：US10265133
申请日：2002-10-07
IPC分类号： C12N1300
摘要： The object of the invention is to provide a method and apparatus for treating membrane-containing material with electrical fields, in vitro, and with an added treating substance. With the method, a plurality of electrodes are arrayed around the material to be treated and are connected to outputs of an electrode selection apparatus. Inputs of the electrode selection apparatus are connected to outputs of a pulse sequence generator. A treating substance is added to the membrane-containing material. Electrical pulses are applied to the electrode selection apparatus and are routed through the electrode selection apparatus in a predetermined, computer-controlled sequence to selected electrodes in the array of electrodes, whereby the membrane-containing material is treated with the added treating substance and with electrical fields. The routing of applied pulses through the electrode selection apparatus to selected electrodes can be done in an enormous number of ways.
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7.发明授权Method and apparatus for the delivery of polynucleotide vaccines to mammalian skin 有权用于将哺乳动物皮肤递送多核苷酸疫苗的方法和装置公开(公告)号：US08979818B2
公开(公告)日：2015-03-17
申请号：US13065135
申请日：2011-03-15
CPC分类号： A61N1/327 , A61K39/12 , A61K2039/53 , A61K2039/54 , A61K2039/70 , A61N1/306 , C07K14/005 , C12N2770/24122 , C12N2770/24134
摘要： An object of the invention is to provide a method and apparatus for the delivery of polynucleotide vaccines into mammalian skin cells to increase T cell response and to reduce pain and discomfort due to long electric waveform application and due to muscle contractions. The method for the delivery of polynucleotide vaccines into mammalian skin cells includes the steps of: (a.) administering a polynucleotide vaccine into the skin at an administration site, (b.) applying a needle electrode to the skin in the vicinity to the administration site, and (c.) applying a sequence of at least three single, operator-controlled, independently programmed, narrow interval electrical waveforms, which have pulse intervals that are less than 100 milliseconds, to deliver the polynucleotide vaccine into the skin cells by electroporation. The sequence of at least three waveforms has one, two, or three of the following characteristics (1) at least two of the at least three waveforms differ from each other in waveform amplitude, (2) at least two of the at least three waveforms differ from each other in waveform width, and (3) a first waveform interval for a first set of two of the at least three waveforms is different from a second waveform interval for a second set of two of the at least three waveforms.
摘要翻译： 本发明的目的是提供一种用于将多核苷酸疫苗递送到哺乳动物皮肤细胞中以增加T细胞应答并减少由于长电波形应用引起的疼痛和不适以及由于肌肉收缩引起的疼痛和不适的方法和装置。 用于将多核苷酸疫苗递送到哺乳动物皮肤细胞中的方法包括以下步骤：（a）在给药部位将多核苷酸疫苗施用于皮肤，（b）将针电极施用于给药的附近的皮肤 站点，以及（c）应用脉冲间隔小于100毫秒的至少三个单个，操作者控制的，独立编程的窄间隔电波形序列，以通过电穿孔将多核苷酸疫苗递送到皮肤细胞中 。 至少三个波形的序列具有以下特征（1）中的一个，两个或三个，所述至少三个波形中的至少两个波形在波形幅度上彼此不同，（2）至少三个波形中的至少两个波形 在波形宽度上彼此不同，以及（3）至少三个波形中的两个的第一组的第一波形间隔与用于至少三个波形中的两个的第二组的第二波形间隔不同。
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8.发明授权Method and apparatus for treating materials with electrical fields having varying orientations 失效用于处理具有不同取向的电场的材料的方法和装置
公开(公告)号：US6117660A
公开(公告)日：2000-09-12
申请号：US242174
申请日：1999-02-10
IPC分类号： C12N13/00
摘要： The object of the invention is to provide a method and apparatus for treating membrane containing material with electrical fields and with an added treating substance. With the method, a plurality of electrodes (121-128) are arrayed around the material to be treated and are connected to outputs of an electrode selection apparatus (110). Inputs of the electrode selection apparatus are connected to outputs of an agile pulse sequence generator. A treating substance is added to the membrane-containing material. Electrical pulses are applied to the electrode selection apparatus and are routed through the electrode selection apparatus in a predetermined, computer-controlled sequence to selected electrodes in the array of electrodes, whereby the membrane containing material is treated with the added treating substance and with electrical fields of sequentially varying directions. The routing of applied pulses through the electrode selection apparatus (110) to selected electrodes (121-128) can be done in an enormous number of ways.
摘要翻译： PCT No.PCT / US97 / 09300 Sec。 371日期1999年2月10日 102（e）1999年2月10日PCT 1997年6月10日PCT公布。 第WO98 / 56893号公报 日期：1998年12月17日本发明的目的是提供一种用电场和附加处理物质处理含膜材料的方法和装置。 利用该方法，将多个电极（121-128）围绕待处理的材料排列并连接到电极选择装置（110）的输出端。 电极选择装置的输入连接到敏捷脉冲序列发生器的输出端。 将处理物质加入到含膜材料中。 将电脉冲施加到电极选择装置，并以预定的计算机控制的顺序通过电极选择装置引导到电极阵列中的选定电极，由此将含有膜的材料用添加的处理物质和电场 顺序变化的方向。 施加的脉冲通过电极选择装置（110）到选定电极（121-128）的布线可以以许多方式进行。
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