Controlled irreversible electroporation

Abstract

Electrical pulses are applied to tissue in a manner which destroys targeted cells such as cancerous cells while sparing non-targeted cells such as nerve cells. The electrical pulses are controlled within ranges for voltage, wattage and duration of application. Multiple pulses or groups of pulses may be applied to obtain a desired result while maintaining any temperature increase below a level which destroys cells.

1 . A method of targeting cancer cells, comprising the steps of:
 (a) identifying cancer cells to be ablated in a target area, wherein the target area comprises indentified nerve tissue;   (b) placing a first electrode and a second electrode such that the target area is positioned between the first and second electrodes;   (c) applying electrical pulses between the first and second electrodes in an amount sufficient to irreversibly electroporate cancer cells in the target area; wherein voltage, wattage and duration of the electrical pulses are maintained within ranges which avoid damage to nerve tissue in the target area.   
     
     
         2 . The method of  claim 1 , further comprising:
 calculating a voltage, wattage and duration of electrical pulse to be applied in a manner so as to avoid damage to nerve tissue in the target area and avoid thermal damage to cells in the target area.   
     
     
         3 . The method of  claim 1 , further comprising:
 determining a size, shape, and relative position of the first electrode and the second electrode in a manner so as to avoid damage to nerve tissue in the target area and avoid thermal damage to cells in the target area.   
     
     
         4 . The method as claimed in  claim 3 , wherein the nerve tissue is surrounded by myelin layers. 
     
     
         5 . The method of  claim 4 , wherein the electrical pulses are applied for a duration in a range of from about 5 microseconds to about 62 seconds, further wherein from about 1 to about 15 pulses are applied. 
     
     
         6 . The method of  claim 5 , wherein the electrical pulses are applied for a period of about 100 microseconds, ±about 10 microseconds. 
     
     
         7 . The method of  claim 5 , wherein about eight pulses of about 100 microseconds each in duration are applied, further wherein the pulses produce a voltage gradient in a range of from about 50 volt/cm to about 8000 volt/cm; and
 wherein the first electrode is placed at about 5 mm to 10 cm from the second electrode.   
     
     
         8 . The method of  claim 1 , further comprising:
 infusing a material into the targeted tissue prior to applying the electrical pulses.   
     
     
         9 . The method of  claim 8 , wherein the material is a chemotherapeutic agent. 
     
     
         10 . The method of  claim 8 , wherein the material is an imaging agent. 
     
     
         11 . The method of  claim 1 , wherein the first electrode and second electrode are circular in shape; and
 wherein the first and second electrodes are positioned with less than 2 cm of each other.   
     
     
         12 . The method of  claim 4 , further comprising:
 monitoring temperature of the targeted tissue; and   adjusting current-to-voltage ratio based on monitored temperature of the target tissue.   
     
     
         13 . The method of  claim 12 , further comprising:
 adjusting the electrical pulses based on real time information of the temperature of the targeted tissue.   
     
     
         14 . The method of  claim 1 , further comprising:
 monitoring temperature of the identified tissue and adjusting the electrical pulses to maintain the temperature at 50° C. or less for a period of time that would avoid thermal damage to cells.   
     
     
         15 . A method of  claim 1 , further comprising:
 adjusting applied voltage, length of pulses, and number of pulses to obtain irreversible electroporation of the cancer cells of the target tissue and minimize damage to cells in the non-target area;   wherein the current-to-voltage ratio is adjusted based on temperature to maintained target tissue temperature at 100° C. or less for a period of time that avoids thermal damage to cells.   
     
     
         16 . The method of  claim 1 , wherein:
 adjusting duration of the applied voltage is in accordance with the current-to-voltage ratio to achieve irreversible electroporation of the cancer cells in the targeted area;   wherein the current-to-voltage ratio is adjusted based on temperature to maintained target tissue temperature at 50° C. or less for a period of time that avoids thermal damage to cells.   
     
     
         17 . A method of treating cancer, comprising:
 (a) identifying nerve tissue in a grouping of biological cells in a target tissue of a living mammal and determining cells in the grouping as being cancer cells;   (b) continuously detecting a ratio of electric current through the targeted tissue to voltage across the targeted tissue as an indication of degree of electroporation of cells in the targeted tissue; and   (c) adjusting a determined magnitude of the applied voltage in accordance with changes in detected magnitude of the current-to-voltage ratio to achieve irreversible electroporation of the cancer cells; and   (d) applying the adjusted voltage to a new target tissue at a point in time after (a), (b) and (c) are completed;   wherein voltage, wattage and duration of the applied electrical pulses of (d) are maintained within ranges which avoid damage to the nerve tissue in the target area.   
     
     
         18 . The method of  claim 17 , wherein step (b) comprises continuously detecting the current-to-voltage ratio in an indication of onset of electroporation of biological cells, and step (c) comprises adjusting the duration of the applied voltage in accordance with continuously detected current-to-voltage ratio to achieve irreversible electroporation of the cancer cells. 
     
     
         19 . The method of  claim 17 , wherein the current-to-voltage ratio is an indication of degree of electroporation averaged over the cells identified as cancer cells, achieving irreversible electroporation of the cancer cells;
 wherein the voltage is applied between two microelectrodes positioned with the cancer cells in between;   wherein temperature of the target tissue is monitored; and   wherein the cancer cells are in a mammal.   
     
     
         20 . The method of  claim 19 , wherein the mammal is a human.