Device and method for single-needle in vivo electroporation

Abstract

Described is a device and method for administration of molecules to tissue in vivo for various medical applications, the device comprising a single hypodermic injection needle and at least two spaced elongate electrodes which provide for the ability, when the needle is inserted into tissue, such as skin or muscle, to pulse tissue with a non-uniform electric field sufficient to cause reversible poration of cells lying along or in close proximity to the track made by the needle upon its insertion into said tissue.

What is claimed: 
     
         1 . A needle electrode device for reversible electroporation of tissue in vivo, comprising:
 an elongate hollow delivery tube capable of penetrating a body tissue, the tube having an outer surface that defines a length extending from a proximal end to a distal tip, the delivery tube having a lumen extending centrally through the delivery tube from the proximal end to the distal tip, wherein the delivery tube further comprises at least one anode and at least one cathode that are each elongate and extend along the length, wherein each of the at least one anode and the at least one cathode defines 1) an exposed portion on the outer surface that extends to the distal tip, and 2) an unexposed portion that extends from the exposed portion toward the proximal end, wherein the anode and the cathode are electrically isolated from one another and maintain a parallel relationship to each other; and   electrically conductable conduits capable of connecting each of the at least one anode and the at least one cathode to an electrical energy source,   wherein when the delivery tube is inserted into tissue and when the at least one anode and the at least one cathode are energized by the energy source, an electric field is generated to reversibly electroporate cells in a treatment zone surrounding the delivery tube so as to allow the cells to take up an active ingredient in a fluid composition delivered through the lumen of the delivery tube.   
     
     
         2 . The needle electrode device of  claim 1 , wherein the unexposed portion of each anode and cathode is insulated. 
     
     
         3 . The needle electrode device of  claim 2 , wherein the unexposed portion of each anode and cathode extend along the outer surface of the delivery tube. 
     
     
         4 . The needle electrode device of  claim 1 , wherein the unexposed portion of each anode and cathode extends internally with respect to the delivery tube. 
     
     
         5 . The needle electrode device of  claim 1 , wherein the length of the outer surface of the delivery tube and respective lengths of the exposed portions of each anode and cathode are collectively configured such that the treatment zone is locatable entirely within muscle tissue. 
     
     
         6 . The needle electrode device of  claim 5 , wherein the respective lengths of the exposed portions of each anode and cathode are collectively configured such that electrode needle device avoids electroporation of dermal layers while electroporating muscle tissue. 
     
     
         7 . The needle electrode device of  claim 5 , wherein the respective lengths of the exposed portions of each anode and cathode are collectively configured such that electrode needle device avoids electroporation of fat cell layers while electroporating muscle tissue. 
     
     
         8 . The needle electrode device of  claim 5 , wherein the length of the outer surface of the delivery tube and the respective lengths of the exposed portions of each anode and cathode are collectively configured such that the treatment zone is locatable entirely within 1) muscle tissue, or 2) dermal layers when the delivery tube is inserted at an acute angle with respect to the surface of the patient's skin. 
     
     
         9 . The needle electrode device of  claim 1 , further comprising a reservoir connectable to the delivery tube and configured to hold a fluidic therapeutic substance in fluid communication with the lumen of the delivery tube. 
     
     
         10 . The needle electrode device of  claim 9 , wherein the reservoir is a syringe, and the needle electrode device further comprises a holding device extending from a planar guide tray, wherein the holding device is configured to hold the syringe at an acute angle relative to the planar guide tray. 
     
     
         11 . The needle electrode device of  claim 10 , wherein the acute angle is in a range from 3 degrees to 25 degrees. 
     
     
         12 . The needle electrode device of  claim 1 , wherein the delivery tube is a needle that defines the lumen, and the lumen is surrounded by an insulating material on which each of the at least one anode and at least one cathode is layered. 
     
     
         13 . The needle electrode device of  claim 1 , further comprising a layer of insulation overlying a proximal portion of the delivery tube, 18 wherein the unexposed portions of each of the at least one anode and at least one cathode extend along the proximal portion of the delivery tube and are coated with the layer of insulation. 
     
     
         14 . The needle electrode device of  claim 1 , wherein the delivery tube comprises a hypodermic needle sized to the gauge of an injection needle of 20 gauge, 21 gauge, 22 gauge, 23 gauge, 24 gauge, 25 gauge, 26 gauge, 27 gauge, 28 gauge and 29 gauge. 
     
     
         15 . The needle electrode device of  claim 14 , wherein the delivery tube is between 3 mm and 1.5 cm in length or between 1.0 cm and 3 cm in length. 
     
     
         16 . The needle electrode device of  claim 1 , further comprising an expandable or contractible reservoir, wherein the reservoir has a variable volume capacity of 0.0 to 0.5 ml, 0.0 to 1 ml, 0.0 to 3 ml, and 0.0 to 5 ml. 
     
     
         17 . The needle electrode device of  claim 1 , wherein the electrical energy source is an electroporation pulse generator. 
     
     
         18 . The needle electrode device of  claim 17 , wherein the generator is capable of generating one or more electric pulses, wherein the one or more electric pulses have:
 an average voltage in a range from about 1 V to about 200 V; and   a current in a range from about 1 mAmp to about 400 mAmps.   
     
     
         19 . The needle electrode device of  claim 17 , wherein the one or more electric pulses have a frequency in a range from about 1 Hz to about 10,000 Hz. 
     
     
         20 . The needle electrode device of  claim 17  wherein the one or more electric pulses each have a time length in a range of about 0.1 ms to about 1000 ms.