Methods, systems, and apparatuses for tissue ablation using electrolysis and permeabilization

• US 10,390,874 B2
• Filed: 11/14/2014
• Issued: 08/27/2019
• Est. Priority Date: 11/14/2013
• Status: Active Grant

• Current Assignee: RM2 Technology LLC
• Original Assignee: RM2 Technology LLC
• Inventors: Rubinsky, Boris, Mikus, Paul, Rubinsky, Liel
• Primary Examiner(s): Peffley, Michael F
• Application Number:
  US15/036,393
• Publication Number:
  US 20160296269A1
• Time in Patent Office: 1,747 Days
• CPC Class Codes: A61B 18/02 by cooling, e.g. cryogenic techniques devices for cooling specific reflex points of the body within cell-life limits A61H39/06
• CPC Class Codes: A61B 18/04 by heating by applying electromagnetic radiation A61B18/18; hyperthermia using electric or magnetic fields, radiation or ultrasound A61N
• 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 18/1492 having a flexible, catheter-like structure, e.g. for heart ablation A61B18/1477 takes precedence
• CPC Class Codes: A61B 18/16 Indifferent or passive electrodes for grounding
• CPC Class Codes: A61B 2018/00333 Breast
• CPC Class Codes: A61B 2018/00404 Blood vessels other than those in or around the heart
• CPC Class Codes: A61B 2018/00434 Neural system
• CPC Class Codes: A61B 2018/00452 Skin
• CPC Class Codes: A61B 2018/00464 Subcutaneous fat, e.g. liposuction, lipolysis
• CPC Class Codes: A61B 2018/00482 Digestive system
• CPC Class Codes: A61B 2018/00517 Urinary bladder or urethra
• CPC Class Codes: A61B 2018/00547 Prostate
• CPC Class Codes: A61B 2018/00577 Ablation
• CPC Class Codes: A61B 2018/00613 Irreversible electroporation reversible electroporation A61N1/327
• CPC Class Codes: A61B 2018/00827 Current
• CPC Class Codes: A61B 2018/00892 Voltage
• CPC Class Codes: A61B 2018/00994 combining two or more different kinds of non-mechanical energy or combining one or more non-mechanical energies with ultrasound
• CPC Class Codes: A61B 2018/0212 using an instrument inserted into a body lumen, e.g. catheter
• CPC Class Codes: A61B 2018/0262 using a circulating cryogenic fluid
• CPC Class Codes: A61B 2018/0293 : using an instrument interstitially inserted into the body, e.g. needle
• CPC Class Codes: A61B 2018/1266 : with DC current output
• CPC Class Codes: A61B 2018/1425 : Needle
• CPC Class Codes: A61B 2018/143 : multiple needles
• CPC Class Codes: A61B 2018/1472 : for use with liquid electrolyte, e.g. virtual electrodes
• CPC Class Codes: A61M 2025/105 : having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 2025/1052 : for temporarily occluding a vessel for isolating a sector
• CPC Class Codes: A61M 2205/054 : with electrotherapy
• CPC Class Codes: A61M 2205/52 : with memories providing a history of measured variating parameters of apparatus or patient
• CPC Class Codes: A61M 25/104 : used for angioplasty
• CPC Class Codes: A61N 1/0502 : Skin piercing electrodes
• CPC Class Codes: A61N 1/205 : for promoting a biological process
• CPC Class Codes: A61N 1/32 : alternating or intermittent currents applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02
• 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: C25B 1/26 : Chlorine; Compounds thereof by simultaneous production of alkali metal hydroxides and chlorine, oxyacids or salts of chlorine C25B1/34
• CPC Class Codes: C25B 11/04 : characterised by the material
• CPC Class Codes: C25B 9/17 : Cells comprising dimensionally-stable non-movable electrodes; Assemblies of constructional parts thereof

Abstract

Example apparatuses and systems are disclosed for providing controlled delivery of electrolysis treatment and cellular permeabilization treatment to a site in tissue. A system disclosed may include an electrode, a power supply, and a controller. The controller may control a charge applied to the electrode to induce a direct current through the aqueous matrix to produce electrolysis products and a voltage to produce electroporation. The duration and magnitude of the charge applied may determine the dose of the products and the degree of the permeabilization of cells in the treatment site. The composition of the electrodes may be chosen in accordance with the desired products produced and electroporation effects. An apparatus is disclosed that may be in the form of electrodes the electrolysis and electrodes for electroporation applied to the tissue. An apparatus is disclosed that may be used for treating internal tissue.

Claims

1. A method for tissue ablation, the method comprising:

permeabilizing cell membranes in the tissue; and

performing electrolysis to deliver electrons to and remove electrons from the tissue thereby generating products of electrolysis in the tissue, wherein said products of electrolysis are toxic to cells in the tissue.

2. The method of claim 1, wherein said permeabilizing comprises performing electroporation.

3. The method of claim 1, wherein said permeabilizing occurs before, during, or after said performing electrolysis, or combinations thereof.

4. The method of claim 1, wherein said permeabilizing comprises performing cryosurgery, freezing, cold-poration, heat-poration, sonic-poration, chemo-poration or combinations thereof.

5. The method of claim 1, wherein said products of electrolysis comprise hypochlorous acid.

6. The method of claim 1, wherein said performing electrolysis comprises applying at least one electrode to the tissue, wherein the products of electrolysis are formed from ions in the tissue using the electrodes to deliver electrons to and remove electrons from the ions in the tissue.

7. The method of claim 1, wherein said performing electrolysis comprises providing an electrical signal using a controller to a device configured to generate the electrons delivered to the tissue, wherein the device is positioned proximate the tissue.

8. The method of claim 7, wherein the controller is coupled to a power supply, and the power supply is configured to provide a current to the device.

9. The method of claim 8, wherein the current delivers the electrons and the electrical signal controls timing and magnitude of the current to generate a sufficient amount of products of electrolysis to ablate permeabilized cells in the tissue.

10. The method of claim 1, wherein said performing electrolysis and permeabilizing cell membranes utilize a same device.

11. The method of claim 10, wherein the same device comprises an electrode.

12. The method of claim 1, wherein said performing electrolysis and permeabilizing cell membranes utilize a same power supply.

13. The method of claim 1, wherein an extent of the tissue ablation is determined, at least in part, by said permeabilizing.

14. The method of claim 1, further comprising measuring a pH in the tissue, wherein the pH is indicative of a desired extent of ablation by products of electrolysis.

15. The method of claim 1, further comprising measuring an electric field through the tissue, wherein the electric field is indicative of permeabilizing of the tissue.

16. The method of claim 1, wherein permeabilizing and performing electrolysis comprise applying an electric field of at least 100 V/cm for a period of time that is equal or less than 30 minutes.

17. The method of claim 1, wherein permeabilizing includes applying an electric field of at least 100 V and wherein performing electrolysis includes applying a direct current of at least 9 mA.

18. The method of claim 17, wherein the electric field is applied for a period of time that is equal or less than 168 seconds.

19. An apparatus for tissue ablation, the apparatus comprising:

a source of products of electrolysis, wherein the source is configured to generate products of electrolysis through an electrochemical reaction of electrolysis by delivering electrons to or removing electrons from ions in the tissue, and the source is positioned proximal the tissue; and

a device configured to permeabilize cell membranes in the tissue.

20. The apparatus of claim 19, wherein the device configured to permeabilize cell membranes in the tissue comprises an electroporation device.

21. The apparatus of claim 19, wherein the device configured to permeabilize cell membranes in the tissue comprises a sonicator.

22. The apparatus of claim 19, wherein the device configured to permeabilize cell membranes in the tissue comprises a cryosurgery device.

23. The apparatus of claim 19, further comprising a device configured to perform at least one of cryosurgery, freezing, cold-poration, heat-poration, sonic-poration, and chemo-poration.

24. The apparatus of claim 19, wherein the source of products of electrolysis comprises two electrodes and the tissue.

25. The apparatus of claim 24, wherein the two electrodes comprise two monopolar needle electrodes, one bipolar or multipolar needle, two surface electrodes, one surface and one needle electrode, two point electrodes, one point electrode and one needle electrode, one point electrode and one surface electrode or combinations thereof.

26. The apparatus of claim 19, wherein the source of products of electrolysis comprises an electrode and wherein the device configured to permeabilize cell membranes also comprises the electrode.

27. The apparatus of claim 19, wherein the tissue comprises a tumor.

28. The apparatus of claim 19, wherein the tissue comprises prostate, breast, blood vessel, urethra, bladder, GI tract, nerve, skin, fat, or combinations thereof.

29. The apparatus of claim 19, further comprising a pump to flush a portion of the products of electrolysis away from the tissue.

30. The apparatus of claim 19, further comprising a reservoir coupled to the source of products of electrolysis for introduction of further compounds.

31. The apparatus of claim 19, wherein the source of products of electrolysis comprises an electrode, and wherein the apparatus further comprises a sensor to monitor pH at the electrode.

32. The apparatus of claim 19, wherein the device is configured to apply an electric field of at least 100 V/cm for a period of time that is equal or less than 30 minutes.

33. The apparatus of claim 19, wherein the device is configured to apply an electric field of at least 100 V and apply a direct current of at least 9 mA.

34. The apparatus of claim 33, wherein the electric field is applied for a period of time that is equal or less than 168 seconds.