INTEGRATION OF VERY SHORT ELECTRIC PULSES FOR MINIMALLY TO NONINVASIVE ELECTROPORATION

• US 20100261994A1
• Filed: 04/09/2010
• Published: 10/14/2010
• Est. Priority Date: 04/09/2009
• Status: Active Grant

• Current Assignee: Virginia Tech Intellectual Properties, Inc. (Virginia Polytechnic Institute and State University)
• Original Assignee: Virginia Tech Intellectual Properties, Inc. (Virginia Polytechnic Institute and State University)
• Inventors: CALDWELL, John, DAVALOS, Rafael, ARENA, Christopher B.
• Granted Patent: US 8,926,606 B2
• Time in Patent Office: Days
• US Class Current: 600/411
• CPC Class Codes: A61B 18/1477 Needle-like probes
• CPC Class Codes: A61B 2018/0016 Energy applicators arranged in a two- or three dimensional array
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation
• CPC Class Codes: A61N 1/0412 Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs
• CPC Class Codes: A61N 1/0424 Shape of the electrode
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The present invention provides methods, devices, and systems for in vivo treatment of cell proliferative disorders. The invention can be used to treat solid tumors, such as brain tumors. The methods rely on non-thermal irreversible electroporation (IRE) or supra-poration to cause cell death in treated tumors. In embodiments, the methods comprise the integration of ultra-short electric pulses, both temporally and spatially, to achieve the desired modality of cell death.

Claims

1. A method of treating a subject suffering from an aberrant cell growth, said method comprising:

implanting an electrode into or adjacent the aberrant growth region within the body of a subject, and

causing multiple electrical pulses to be emitted from the electrode into the aberrant growth region in ten microsecond or shorter pulses to cause predominantly non-thermal killing of aberrantly growing cells by IRE.

2. The method of claim 1, wherein the pulses are between 10,000 nanoseconds and 1 picosecond.

3. The method of claim 1, wherein two or more electrodes are used in the method and are provided as part of a single device.

4. The method of claim 1, wherein two or more electrodes are used in the method.

5. The method of claim 4, further comprising positioning the electrodes at a distance apart from each other to create custom treatment area shapes through varying electrode activation patterns.

6. The method of claim 1, wherein the aberrant cell growth is a neoplasia.

7. The method of claim 6, wherein the neoplasia is leukemia or pancreatic cancer.

8. The method of claim 1, wherein the subject is a human.

9. The method of claim 1, wherein the implanted electrode is a current input electrode and wherein a current return electrode is implanted within the body of the subject at a site adjacent to or distant from the aberrant growth region, or is provided external to the subject.

10. The method of claim 1, wherein the implanted electrode is a return electrode and wherein a current input electrode is implanted within the body of the subject at a site adjacent to or distant from the aberrant growth region, or is provided external to the subject.

11. The method of claim 1, wherein the method results in a reduction in cell proliferation of the aberrant cells.

12. The method of claim 1, wherein the method results in a reduction in the size of a tumor.

13. The method of claim 12, wherein the method results in ablation of the tumor.

14. The method of claim 1, wherein causing multiple electrical pulses to be emitted from the electrode comprises emitting multiple electric pulses such that the temporal and spatial summation of such pulses results in the generation of an electric field of about 500 V/cm to 2500 V/cm for 10000 microseconds or less to induce IRE.

15. The method of claim 1, wherein causing multiple electrical pulses to be emitted from the electrode comprises emitting multiple electric pulses such that the temporal and spatial summation of such pulses results in the generation of an electric field of about 1 kV/cm to 50 kV/cm for 1000 nanoseconds or less to induce supra-poration in addition to IRE.

16. The method of claim 1, wherein the individual electric pulses are monophasic.

17. The method of claim 1, wherein the individual electric pulses are biphasic.

18. The method of claim 1, wherein a train of monophasic pulses is delivered in one direction, followed by a subsequent pulse train of opposite polarity.

19. The method of claim 1, wherein the waveforms or the electric pulses are triangular, square, sinusoidal, exponential, or trapezoidal.

20. The method of claim 1, wherein the electrode is connected to a system for employing electrical impedance tomography (EIT), computer tomography (CT), Magnetic Resonance Imaging (MRI), or ultrasound to image the tissue prior to treatment by applying small alternating currents that themselves do not damage the tissue.

21. A method of treating a subject suffering from an aberrant cell growth, said method comprising:

contacting the subject with a first electrode,

placing at least two additional electrodes outside the subject'"'"'s body at positions that permit electrical charges to be delivered to the aberrant cell growth, and

causing multiple electrical pulses to be emitted from one or more of the electrodes into the aberrant growth region in ten microsecond or shorter pulses to cause predominantly non-thermal killing of aberrantly growing cells by IRE.

22. The method of claim 21, wherein contacting comprises contacting the first electrode with the skin of the subject.

23. The method of claim 21, wherein contacting comprises implanting the first electrode at a site in the subject'"'"'s body that is adjacent to the aberrant cell growth.

24. The method of claim 21, which is a method of delivering an electric pulse through a layer using short pulses.

25. The method of claim 21, wherein the layer is bone, muscle, fat, connective tissue, nervous tissue, or an endothelial layer.

26. The method of claim 21, wherein the pulses induce a combination of both IRE and supra-poration.

27. A method of treating a subject suffering from an aberrant growth, said method comprising:

implanting an electrode into or adjacent the aberrant growth, and

causing multiple electrical pulses to be emitted from the electrode into the aberrant growth in ten microsecond or shorter pulses,

wherein the electrical pulses cause reversible electroporation of cells of the aberrant growth and/or cells adjacent the aberrant growth, which results in uptake of bioactive substances into the treated cells.