Devices for needle-free injection and electroporation

Abstract

Methods are proved for introducing a biologically active agent into cells of a subject by introducing the agent in a form suitable for electrotransport into a region of tissue of the subject using one or more needle-free injectors, and applying a pulsed electric field to the region of tissue, thereby causing electroporation of the region of tissue. The combination of needle-free injection and electroporation is sufficient to introduce the agent into cells in skin, muscle or mucosa. For example, the region of tissue can be contacted with two oppositely charged injectors, one acting as the donor electrode and one acting as the counter electrode, or a single injector and one or more electrodes can be used. In addition, needle-free injection may be used in combination with suitable non-invasive electrode configurations. The active agents delivered into cells using the invention method can be small molecules, polynucleotides, polypeptides, and the like.

1 - 47 . (canceled)  
     
     
         48 . An electroporation device, comprising: 
 a. a needle-free injector configured to serve as a first electroporation electrode when positioned in contact with a tissue of a patient, wherein the needle-free injector injects at least one liquid jet to introduce an agent into or beneath the tissue;    b. a second electroporation electrode disposed in spaced relation to the first electroporation electrode; and    c. electrical connections to electrically connect the needle-free injector and the second electroporation electrode with an electrical source for generating electrical current used to effect electroporation.    
     
     
         49 . An electroporation device according to  claim 48  wherein the second electroporation electrode comprises a ring electrode.  
     
     
         50 . An electroporation device according to  claim 48 , wherein the second electroporation electrode comprises an array of electrodes.  
     
     
         51 . An electroporation device according to  claim 50 , wherein said array of electrodes comprises a micropatch electrode.  
     
     
         52 . An electroporation device according to  claim 51 , wherein said micropatch electrode comprises a meander electrode.  
     
     
         53 . An electroporation device according to  claim 48 , wherein said electrodes further comprise timing sensors.  
     
     
         54 . An electroporation device according to  claim 48  wherein the second electroporation electrode is also a needle-free injector.  
     
     
         55 . An electroporation device according to  claim 48  comprising a plurality of needle-free injectors, each of which is configured to serve as an electroporation electrode, and wherein the device comprises electrical connections to electrically connect each electroporation electrode with the electrical source.  
     
     
         56 . An electroporation device according to  claim 48  wherein the needle-free injector serves as the first electroporation electrode by injecting a conductive fluid comprising the agent and specific resistivity sufficient to allow application of an electrical field to effect electroporation of the tissue.  
     
     
         57 . An electroporation device according to  claim 56 , wherein the liquid jet acts as an electrode.  
     
     
         58 . An electroporation device according to  claim 56 , wherein the conductive fluid is contained in a partially ionized solvent.  
     
     
         59 . An electroporation device according to  claim 56 , wherein the application of an electric field takes place without the device touching the tissue.  
     
     
         60 . An electroporation device according to  claim 56 , wherein the agent is in a liquid and the injector forces the liquid into the tissue as a conductive or essentially non-conductive liquid jet.  
     
     
         61 . An electroporation device according to  claim 48  wherein the electrical source is a pulse generator.  
     
     
         62 . An electroporation system comprising the electroporation device of  claim 48  in electrical communication with an electrical source used to effect electroporation.  
     
     
         63 . An electroporation system according to  claim 62 , wherein the current generated by the electrical source is a wave pulse selected from the group consisting of a square, rectangular, triangular, and an exponential decay wave pulse.  
     
     
         64 . An electroporation system according to  claim 63 , wherein the pulse is monopolar or bipolar.  
     
     
         65 . An electroporation system according to  claim 63 , wherein the pulse is monopolar or bipolar.  
     
     
         66 . An electroporation system according to  claim 62 , wherein the electrical source is a pulse generator.  
     
     
         67 . An electroporation device, comprising: 
 a. an array electrode comprising (i) at least one positive electrode and at least one negative electrode, wherein the electrodes are configured to generate an electrical field to effect electroporation of a tissue of a patient when energized, and (ii) an opening through which a needle-free injector can be inserted, wherein the needle-free injector injects a liquid jet comprising an agent into or beneath the tissue; and    b. electrical connections to electrically connect the array electrode with an electrical source for generating electrical current used to generate the electrical field to effect electroporation.