Electroporation to interrupt blood flow

Abstract

A method for disrupting blood flow to 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 vessels supplying blood to the undesirable tissue and through the application of electrical pulses causing blood flow disruption. 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 process may further comprise monitoring blood flow and/or infusion of a material such as a chemotherapeutic agent or marker into the blood.

1 .- 36 . (canceled) 
   
   
       37 . A device for disrupting blood flow, comprising:
 first and second electrodes that position a blood vessel to be disrupted therebetween;   a voltage generator means that applies a voltage between the first and second electrodes in a manner which provides a predetermined electric field around the blood vessel for a time sufficient to disrupt blood flow through the vessel.   
   
   
       38 . The device of  claim 37 , wherein the generator means generates pulses of 100 microseconds ±about 10 microseconds at a voltage gradient in a range of from about 50 volt/cm to about 8000 volt/cm. 
   
   
       39 . The device of  claim 37 , further comprising:
 a means for adjusting the voltage and pulse duration of the generator means to obtain blood flow disruption.   
   
   
       40 . The device of  claim 37 , further comprising:
 a means for monitoring blood flow.   
   
   
       41 .- 53 . (canceled) 
   
   
       54 . The device of  claim 37 , wherein the generator is designed to apply electrical pulses for a duration in a range of from about 5 microseconds to about 62 seconds. 
   
   
       55 . The device of  claim 37 , wherein the generator is designed to apply electrical pulses for a period of about 100 microseconds, ±about 10 microseconds. 
   
   
       56 . The device of  claim 37 , wherein the generator is designed so that on activation it applies from about 1 to about 15 pulses. 
   
   
       57 . The device of  claim 37 , wherein the generator is designed so that on activation it applies about eight pulses of about 100 microseconds each in duration. 
   
   
       58 . The device of  claim 37 , wherein the generator is designed so that on activation it applies pulses that produce a voltage gradient in a range of from about 50 volt/cm to about 8000 volt/cm. 
   
   
       59 . The device of  claim 37 , wherein the first electrode is positioned at about 5 mm to 10 cm from the second electrode. 
   
   
       60 . The device of  claim 37 , further comprising:
 a monitor for monitoring blood flow in blood vessels.   
   
   
       61 . The device of  claim 60 , further comprising:
 a means for adjusting the electrical pulses based on real time information of the monitored blood flow.   
   
   
       62 . The device of  claim 37 , further comprising:
 a monitor for monitoring temperature of the identified tissue; and   a means for adjusting the electrical pulses to maintain the temperature at 100° C. or less.   
   
   
       63 . The device of  claim 62 , wherein the monitor maintains the temperature at 50° C. or less. 
   
   
       64 . A device of  claim 37 , further comprising:
 a means for adjusting applied voltage, length of pulses, and number of pulses to obtain blood flow disruption to the target area thereby minimizes damage to non-target tissue.   
   
   
       65 . The device of  claim 37 , further comprising:
 a means for adjusting duration of applied voltage is in accordance with current-to-voltage ratio to achieve blood flow disruption to a targeted area.   
   
   
       66 . The device of  claim 65 , wherein the means for adjusting, adjusts the current-to-voltage ratio based on temperature to maintain target tissue temperature at 100° C. or less. 
   
   
       67 . The device of  claim 65 , wherein the means for adjusting, adjusts the current-to-voltage ratio based on temperature to maintain target tissue temperature at 50° C. or less. 
   
   
       68 . The device of  claim 37 , further comprising:
 a means for adjusting current-to-voltage ratio connected to and interactive with a means for monitoring blood flow.   
   
   
       69 . The device of  claim 37 , a means for determining an indication of degree of electroporation averaged over cells identified as cancer cells. 
   
   
       70 . The device of  claim 37 , wherein the electrodes are microelectrodes.