High frequency electroporation for cancer therapy

• US 10,292,755 B2
• Filed: 06/20/2016
• Issued: 05/21/2019
• Est. Priority Date: 04/09/2009
• Status: Active Grant

• Current Assignee: Virginia Tech Intellectual Properties, Inc.
• Original Assignee: Virginia Tech Intellectual Properties, Inc.
• Inventors: Arena, Christopher B., Davalos, Rafael V., Sano, Michael B.
• Primary Examiner(s): Fowler, Daniel W
• Application Number:
  US15/186,653
• Publication Number:
  US 20160287314A1
• Time in Patent Office: 1,065 Days
• CPC Class Codes: A61B 18/14 Probes or electrodes therefor
• CPC Class Codes: A61B 2017/00159 Pulse shapes
• CPC Class Codes: A61B 2017/00172 Pulse trains, bursts, intermittent continuous operation
• CPC Class Codes: A61B 2018/0016 Energy applicators arranged in a two- or three dimensional array
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation reversible electroporation A61N1/327
• CPC Class Codes: A61B 2018/00732 Frequency
• CPC Class Codes: A61B 2018/00761 Duration
• CPC Class Codes: A61B 2018/00767 Voltage
• CPC Class Codes: A61B 2018/126 bipolar
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation

Abstract

The present invention relates to the field of biomedical engineering and medical treatment of diseases and disorders. Methods, devices, and systems for in vivo treatment of cell proliferative disorders are provided. In embodiments, the methods comprise the delivery of high-frequency bursts of bipolar pulses to achieve the desired modality of cell death. More specifically, embodiments of the invention relate to a device and method for destroying aberrant cells, including tumor tissues, using high-frequency, bipolar electrical pulses having a burst width on the order of microseconds and duration of single polarity on the microsecond to nanosecond scale. In embodiments, the methods rely on conventional electroporation with adjuvant drugs or irreversible electroporation to cause cell death in treated tumors. The invention can be used to treat solid tumors, such as brain tumors.

Claims

1. A method of ablating tissue cells by non-thermal irreversible electroporation comprising:

positioning one or more electrodes near a target area containing target tissue cells to be ablated;

applying a plurality of electrical pulses to the target area through the positioned electrodes by applying pulses at a frequency rate of 50 kHz or higher with each electrical pulse having a pulse width of 10 microseconds or less, so as to ablate the target tissue cells by non-thermal irreversible electroporation.

2. The method of claim 1, wherein the step of applying includes applying the plurality of electrical pulses at the frequency rate of between 50 kHz and 2 MHz, inclusive.

3. The method of claim 1, wherein the step of applying includes applying the plurality of electrical pulses at the frequency rate of between 250 kHz and 2 MHz, inclusive.

4. The method of claim 1, wherein the step of positioning includes non-invasively positioning the one or more electrodes near the target area.

5. The method of claim 1, wherein the pulse width of a single electrical pulse is at least 100 nanoseconds.

6. The method of claim 1, wherein the pulse width of a single electrical pulse is in the range of 250 nanoseconds to 2 microseconds, inclusive.

7. The method of claim 1, wherein the step of applying includes applying a plurality of bipolar electrical pulses.

8. The method of claim 1, wherein the step of applying includes applying a plurality of bipolar bursts of electrical pulses with multiple pulses in a single phase before a polarity switch.

9. The method of claim 1, wherein the electrical pulses are square, ramp, sinusoidal, exponential, or trapezoidal.

10. The method of claim 1, wherein the step of applying includes applying a burst of electrical pulses which is sufficient to cause a transmembrane potential (TMP) of the target tissue cells to rise above a critical threshold (CT) for inducing electroporation while a single electrical pulse in the burst of electrical pulses is insufficient to cause the TMP of the target tissue cells to rise above the CT.

11. The method of claim 1, wherein the step of applying includes applying a plurality of electrical pulses wherein each electrical pulse is sufficient to cause a transmembrane potential (TMP) of the target tissue cells to rise above a critical threshold (CT) for inducing electroporation.

12. The method of claim 1, wherein the step of applying includes applying a burst of electrical pulses which is sufficient to cause a transmembrane potential (TMP) of the target tissue cells to rise above a critical threshold for inducing irreversible electroporation (CTIRE) while a single electrical pulse in the burst of electrical pulses is insufficient to cause the TMP of the target tissue cells to rise above the CTIRE.

13. The method of claim 12, wherein the CTIRE is about 1 Volt.

14. The method of claim 1, wherein the step of applying includes applying a plurality of electrical pulses wherein each electrical pulse is sufficient to cause a transmembrane potential (TMP) of the target tissue cells to rise above a critical threshold (CT) for inducing irreversible electroporation.

15. The method of claim 1, wherein the step of applying includes applying the electrical pulses at 2500 V/cm or lower.

16. The method of claim 1, wherein the step of applying includes controlling voltage and pulse width of the electrical pulses to reduce tissue stimulation sufficiently to perform tissue ablation without using general anesthesia.