System and method for creating radio-frequency energy electrical membrane breakdown for tissue ablation

• US 10,154,869 B2
• Filed: 08/04/2014
• Issued: 12/18/2018
• Est. Priority Date: 08/02/2013
• Status: Active Grant

• Current Assignee: ImmunSYS, Inc.
• Original Assignee: ImmunSYS, Inc.
• Inventors: Onik, Gary M., Miessau, James A.
• Primary Examiner(s): Peffley, Michael
• Assistant Examiner(s): ZINK, AMANDA L
• Application Number:
  US14/451,333
• Publication Number:
  US 20150150618A1
• Time in Patent Office: 1,597 Days
• CPC Class Codes: A61B 18/00 Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body eye surgery A61F9/007; ear surgery A61F11/00
• CPC Class Codes: A61B 18/12 by passing a current through the tissue to be heated, e.g. high-frequency current
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/00761 Duration
• CPC Class Codes: A61B 2018/00821 measured by a thermocouple
• CPC Class Codes: A61B 2018/00988 Means for storing information, e.g. calibration constants, or for preventing excessive use, e.g. usage, service life counter
• CPC Class Codes: A61B 2018/143 multiple needles

Abstract

A method of non-thermally ablating undesirable tissue in the body by application of pulsed, bi-polar, instant charge reversal electrical fields of sufficient energy to cause complete and immediate cell membrane rupture and destruction. Energy is delivered through radio frequency pulses of particular frequencies, wave characteristics, pulse widths and pulse numbers, such that enhanced physical stresses are placed on the cell membrane to cause its immediate and complete destruction thereby spilling the entire cell content and membrane constituents into the extracellular space without denaturing proteins so as to enable an immunological response to destroy and remove the target tissue and similarly marked tissue elsewhere in the subject.

Claims

1. A method of ablating undesirable soft tissue in a living subject, comprising the steps of:

identifying a location of said soft tissue within said subject;

determining a position, of at least one electrode relative to said soft tissue;

introducing said at least one electrode to said position within said subject, said electrode electrically connected to a controller for controlling the delivery of electric pulses to said electrode, said controller comprising an electric pulse generator;

applying to said soft tissue an electric field sufficient to cause electrical membrane breakdown of a cell membrane of a plurality of cells of said soft tissue to cause immediate spillage of all intracellular components into an extracellular space and exposure of an internal constituent part of said cell membrane to said extracellular space, said electric field applied to said soft tissue by delivering from said pulse generator to said at least one electrode at least one bi-polar pulse train configured to cause said electrical membrane breakdown, said bi-polar pulse train comprising at least two bi-polar electric pulses, each said bi-polar electric pulse in said bi-polar pulse train being separated by an inter pulse burst interval during which no voltage is applied to said at least one electrode;

wherein a voltage of each of said bi-polar electric pulses is from 0.5 kV to 10 kV; and

wherein a tissue change, cellular membrane destruction and cell death are visually observable in a sample of said undesirable soft tissue taken immediately after applying said electric field to said soft tissue; and

farther comprising the steps of,

after applying said electric field to said soft tissue by delivering said bi-polar pulse train, immediately biopsying a portion of said soft tissue to determine an efficacy of said ablation;

if said efficacy exceeds a pre-determined threshold, ceasing said ablation of undesirable soft tissue; and

if said efficacy does not exceed said pre-determined threshold, delivering from said pulse generator to said at least one electrode at least one additional bi-polar electric pulse so as to apply to said soft tissue a second electric field.

2. The method of claim 1 wherein a frequency of said electric field is from 14.2 kHz to less than 500 kHz.

3. The method of claim 2 wherein said frequency of said electric field is from 100 kHz to 450 kHz.

4. The method of claim 2 wherein said voltage over time of each of said bi-polar electric pulses traces a square waveform for a positive and negative component of a polarity oscillation.

5. The method of claim 2 wherein said voltage of each of said bi-polar electric pulses is characterized by waveforms with an instant charge reversal, between the positive and negative charge of each cycle.

6. The method of claim 1 wherein the duration of each of said at least one bi-polar electric pulses is from 100-1000 μ

s.

7. The method of claim 1, wherein said determining step further comprises the steps of estimating or measuring the dielectric constant and the conductivity of said soft tissue.

8. The method of claim 1, further comprising the step of configuring said bi-polar pulse train delivered to said at least one electrode from said pulse generator such that said electric field causes no clinically significant thermal damage to said soft tissue.

9. The method of claim 8, wherein said bi-polar pulse train is configured such that said field causes a temperature of said soft tissue to rise to not more than 50 degrees Celsius.

10. The method of claim 1, further comprising at least one additional bi-polar electric pulse to form a second bi-polar pulse train, wherein said second bi-polar pulse train is comprising a second series of not less than 100 bi-polar electric pulses configured so that said second electric field is sufficient to cause electrical membrane breakdown of said cell membrane of a plurality of cells of said soft tissue.

11. The method of claim 1, further comprising the step of introducing a temperature probe proximal to said at least one electrode, said probe operatively connected to said controller and reporting a temperature reading to said controller, said controller controlling varying at least one character of said at least one bi-polar electric pulse in response to said reported temperature.

12. The method of claim 11, wherein said temperature probe is a thermocouple.

13. The method of claim 11, wherein said temperature probe is integral to said at least one electrode and introduced therewith.

14. The method of claim 11, wherein said bi-polar pulse train comprises a series of not less than 100 bi-polar electric pulses, each of said bi-polar electric pulses in said bi-polar pulse train being separated by an inter pulse burst interval during which no voltage is applied to said at least one electrode;

and further comprising the steps of storing in a memory of said controller at least one temperature set-point; and

altering by said controller for at least a portion of said series at least one of a pulse duration, said inter pulse burst interval and a total number of bi-polar electric pulses in said bi-polar pulse train in response to said temperature reading reported to said controller from said probe exceeding said set point.

15. The method of claim 14, further comprising the step of initiating said altering step in response to said temperature reported by said probe falling below said set-point.

16. The method of claim 14, wherein said altering step comprises reducing said pulse duration.

17. The method of claim 15, wherein said altering step comprises increasing said inter pulse burst interval.

18. The method of claim 16, wherein said altering step comprises reducing the number of bi-polar electric pulses in said bi-polar pulse train.

19. The method of claim 1, further comprising the steps of

storing in a memory of a controller at least one maximum current set-point, said controller controlling said delivery of said at least two bi-polar electric pulses;

determining by said controller a current through said at least one electrode; and

reducing said voltage of said at least two bi-polar electric pulses delivered to said at least one electrode when said current equals said maximum current set-point whereby said current is prevented from exceeding said set point.

20. The method of claim 1 wherein said intracellular components comprises a cellular antigen and said internal constituent part of said cell membrane further comprises an antigen specific to, said cell membrane;

and

further comprising the step of administering to said subject an immunologic response enhancing drug to increase said immunologic process of said subject which is activated to remove said, intracellular components and internal constituent part of said cell membrane from said extracellular space.

21. The method of claim 20 wherein said immunologic response enhancing drug blocks inhibition of the CTLA-4 inhibitory signal of cytotoxic lymphocytes.

22. The method of claim 20 wherein said immunologic response enhancing drug is administered by one of intravenously, orally or intramuscularly.

23. The method of claim 20 wherein said immunologic response enhancing drug is injected directly into or adjacent to undesirable soft tissue before or after said step of applying to said soft tissue an electric field.

24. The method of claim 20 wherein said immunologic response enhancing drug is comprised of autologous dendritic cells.

25. The method of claim 20 wherein said immunologic response enhancing drug binds to S100A9 and modulating regulatory myeloid cell functions.

26. The method of claim 20 wherein said immunologic response enhancing drug is comprised of autologous dendritic cells.

27. The method of claim 1, wherein said bi-polar pulse train is a series of not less than 100 bi-polar electric pulses.

28. A method of ablating undesirable soft tissue in a living subject, comprising the steps of:

identifying a location of said soft tissue within said subject;

determining based on a tissue type of said soft tissue a minimum energy profile necessary to be applied to a cell of said soft tissue to cause cell membrane rupture by electrical membrane breakdown;

determining a position of at least one electrode relative to said cell mass;

introducing said at least one electrode to said position within said subject, said electrode electrically connected to a controller for controlling the delivery of electric pulses to said electrode, said controller comprising an electric pulse generator;

determining based on said minimum energy profile and said position of said at least one electrode an electric field strength necessary to apply to said cell mass said minimum energy profile;

determining based on said electric field strength a bi-polar electric pulse train profile having not less than 100 pulses, said pulse train profile characterized by a pulse number, pulse duration and inter pulse burst intervals, said pulses each having a frequency and a voltage, said voltage characterized by an instantaneous reversal of polarity;

delivering from said pulse generator to said at least one electrode by said controller a series of electric pulses according to said electric pulse train profile whereby a pulsed electric field is generated, said field applying sufficient energy to a plurality of said cells of said soft tissue to cause cell death by electrical membrane breakdown.