VARIABLE CURRENT DENSITY SINGLE NEEDLE ELECTROPORATION SYSTEM AND METHOD

• US 20110009807A1
• Filed: 07/14/2010
• Published: 01/13/2011
• Est. Priority Date: 01/17/2008
• Status: Active Grant

• Current Assignee: Inovio Pharmaceuticals, Inc.
• Original Assignee: Genetronics, Inc. (Inovio Pharmaceuticals, Inc.)
• Inventors: KJEKEN, Rune, LIN, Feng, KEMMERRER, Stephen Vincent, RABUSSAY, Dietmar, KARDOS, Thomas Joseph
• Granted Patent: US 10,610,684 B2
• Time in Patent Office: Days
• US Class Current: 604/21
• CPC Class Codes: A61N 1/325 for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

This invention comprises an improved electroporation electrode system comprising a single needle and a ring or donut shaped electrode wherein the difference in surface area of the electrodes provide for a substantial reduction of current density near the surface of the treated tissue and a more concentrated current density sufficient for electroporation only in tissues adjacent to the terminal portion of the single needle electrode. Thus, this invention provides for targeting specific tissue for electroporation and also should provide for lessening the sensation of electric current in the treated tissue.

Claims

1. An electroporation system for delivering a molecule into cells of a mammal comprising:

a) a geometric planar ring electrode;

b) a tissue piercing elongate electrode having a proximal and a distal end, said elongate electrode having a nonconductive portion thereof, said nonconductive portion lying between said proximal end and between about 2.5 and at least 0.1 cm from the distal end, said nonconductive portion comprising either an insulator coating on said elongate electrode or a nonconductive material;

c) a housing associated with said ring and elongate electrodes, said housing covering electronic circuitry in electrical communication with said ring and elongate electrodes, at least one capacitor in electrical communication with said circuitry, and an actuator for driving said elongate electrode in a linear movement of a travel length between 0.5 and 4 cm;

d) a charging unit for charging said capacitor; and

e) a computer in electrical communication with said charging unit, said computer comprising software capable of performing programming functions for said system.

2. The system of claim 1 wherein said ring electrode is electrically isolatable into two electrically conductive halves.

3. The system of claim 2 further comprising circuitry for sensing electrical resistance between each of said halves of said ring electrode and a tissue surface.

4. The system of claim 1 further comprising circuitry for sensing a pressure applied to said ring electrode against a tissue surface.

5. The system of claim 1 wherein said geometric shape of the ring electrode is selected from the group consisting of donut, oval, donut circle, isosceles triangle donut, equilateral triangle donut, a square donut, rectangular donut, a pentagonal donut and a hexagonal donut.

6. The system of claim 5 wherein said ring electrode has a surface area for conducting current proportional to the surface area of said elongate electrode, said proportion of ring:

elongate electrodes surface area ratios selected from the group consisting of 5;

1, 10;

1, 100;

1, and 1000;

1.

7. The system of claim 1 wherein said elongate electrode is tubular and capable of channeling a fluid medium from said proximal end to said distal end, said proximal end being in fluid communication with a reservoir and said distal end having a plurality of apertures positioned along a length of said electrode, said length comprising between about 1.0 and 1.5 cm of said distal portion of said electrode.

8. The system of claim 7 wherein said apertures have a diameter selected from the group consisting of 120 microns, 100 microns, 90 microns, 80 microns, 70 microns, 60 microns, 50 microns, 40 microns, 30 microns and 20 microns.

9. The system of claim 8 wherein the number of said plurality of apertures is selected from the group of between 10 and 100 apertures per centimeter and between 20 and 60 apertures per centimeter of electrically conductive elongate electrode length.

10. The system of claim 9 wherein said actuator is selected from a motor, a mechanically driven actuator and an animatedly driven actuator.

11. The system of claim 10 wherein said acutator is capable of driving both said elongate electrode linear motion and a fluid medium from a reservoir through a lumen in said elongate electrode to and out a plurality of ports at a distal portion of said elongate electrode.

12. The system of claim 1 wherein said elongate electrode is a negative electrode.

51. The system of claim 11 wherein said driving creates a pressure that allows said fluid medium to pass through each aperture at equivalent flow dynamics such that a uniform volume of fluid is ejected about the electrode.

13. A variable current density electrode system for in vivo electroporation comprising:

a) a geometric planar ring electrode;

b) a partially insulated elongate needle electrode wherein said electrode is electrically conductive along a portion of one end thereof;

c) a surface area ratio between said ring electrode and elongate electrode selected from the group consisting of a range between 1000;

1 and 5;

1;

d) a circuitry for connecting said elongate and ring electrodes with a power source for energizing said electrodes,

characterized in that when said electrode system is activated by providing an electric pulse in a body tissue, electric current density in said tissue at or near said needle electrode is higher than current density in said tissue at or near said ring electrode.

14. The variable current density electrode system of claim 13 wherein said ring electrode has a surface area of between 1 cm² and 100 cm².

15. The system of claim 13 wherein said needle electrode has an electrically conductive length of between 0.01 cm and 2.5 cm.

16. The system of claim 15 wherein said needle electrode has an electrically conductive surface area between 0.05 and 1.00 cm².

17. The system of claim 13 wherein said partial insulation on said electrode is between a proximal end and to within about 0.1 to 2.5 cm of a distal end thereof.

18. The system of claim 17 wherein said insulation is selected from group consisting of plastic, paralene, polytetrafluoroethylene and epoxy.

19. The system of claim 13 wherein said ring is electrically isolatable into two electrically equivalent conductive portions.

20. The system of claim 13 wherein said ring electrode is charged with a positive charge and wherein said elongate needle electrode is charged with a negative charge.

21. The system of claim 20 wherein said negative charged elongate electrode results in negligible shedding of metal ions from said electrode into said body tissue upon discharge of an electroporative pulse into said tissue.

22. The system of claim 19 wherein said ring has a geometric shape selected from the group consisting of donut, oval, donut circle, isosceles triangle donut, equilateral triangle donut, a square donut, rectangular donut, a pentagonal donut and a hexagonal donut.

23. The system of claim 13 wherein said elongate electrode is tubular and capable of channeling a fluid medium from a reservoir, said electrode having a plurality of apertures positioned along a length of said electrode, said length comprising between about 1.0 and 1.5 cm of a distal portion of said electrode.

24. The system of claim 23 wherein said apertures have a diameter selected from the group consisting of 120 microns, 100 microns, 90 microns, 80 microns, 70 microns, 60 microns, 50 microns, 40 microns, 30 microns and 20 microns.

25. The system of claim 24 wherein said plurality of apertures is between 20 and 60 per centimeter of electrically conductive elongate electrode length.

26-34. -34. (canceled)

35. A method of delivering a therapeutic substance to a predetermined tissue type comprising:

providing at least one tissue penetrating delivery tube in fluid communication with a source of said therapeutic substance, driving said tube(s) into in vivo tissue wherein said tube, if singular, has two electric poles associated therewith and if more than one tube each has an electrically conductive pole therewith, and while driving said tube(s) into said tissue, sensing electric resistance of said tissue between said electric poles at between 0.1 mm and 2 mm increments of driving distance, wherein when said resistance sensing senses a tissue resistance of a predetermined value, the therapeutic substance is delivered to the tissue through said delivery tube(s).

36. The method of claim 35 wherein said resistance sensing uses a voltage of between 1 and 10 volts.

37. The method of claim 35 wherein said resistance sensing uses a pulse duration of between 1 microsecond and 1 second.

38. The method of claim 37 wherein said pulse duration is 20 milliseconds.

39. The method of claim 35 wherein said resistance sensing takes measurements at between 0.1 and 0.25 mm depth increments into the tissue to a total depth of about 2 cm.

40. The method of claim 35 wherein said predetermined resistance value is set to a reading of 500 ohms at an insertion depth of 4 mm at which point therapeutic substance is delivered.

41. The method of claim 35 wherein said predetermined resistance value is set to a reading of 300 ohms at an insertion depth of 8 mm at which point therapeutic substance is delivered.

50. The method of claim 35 wherein two parallel electrodes are used to sense tissue resistance.

42-49. -49. (canceled)