Method and apparatus for in vivo electroporation of remote cells and tissue

• US 5,389,069 A
• Filed: 09/17/1993
• Issued: 02/14/1995
• Est. Priority Date: 01/21/1988
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Weaver, James C.
• Primary Examiner(s): Lewis, Ralph A.
• Application Number:
  US08/122,809
• Time in Patent Office: 515 Days
• Field of Search: 604/20, 604/21, 604/49, 604/51, 604/52, 128/784, 128/786, 435/173.6
• US Class Current: 604/21
• CPC Class Codes: A61B 5/14514 using means for aiding extraction of interstitial fluid, e.g. microneedles or suction
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61K 41/0047 Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• 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: C07K 14/82 Translation products from oncogenes
• CPC Class Codes: C12M 35/02 Electrical or electromagnetic means, e.g. for electroporation or for cell fusion
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

A method and apparatus is disclosed for causing electroporation of remote cells and tissue, in vivo. The method includes directing an electrically conductive penetrator into an organism to a point which is approximate to the cells and/or tissue. An electrode is disposed at a surface of the organism, whereby a voltage applied between the electrically conductive penetrator and the electrode will cause electroporation of the cells and/or tissue. A voltage is applied between the electrically conductive penetrator and the electrode in an amount sufficient to cause electroporation of the cell or tissue. The method can also include treating remote tissue, in vivo, with a chemical agent, wherein the chemical agent is disposed in the organism in an amount sufficient to treat the cell or tissue during electroporation.

Claims

1. A method for treating at least one cell, in vivo, comprising the steps of:

a) directing a penetrator into an organism, said penetrator including a first electrode, and an opening through which a chemical agent can be injected into the organism proximate to the cell to be treated;

b) placing a second electrode where the cell and the opening of the penetrator are between the first and second electrodes;

c) injecting the chemical agent into the organism through the penetrator in an amount sufficient to treat the cell during electroporation of the cell; and

d) applying a voltage between the first and second electrodes in an amount sufficient to cause electroporation of at least a portion of the cell, whereby the chemical agent migrates across the cell membrane, thereby treating the cell.

2. A method of claim 1 wherein the chemical agent is injected into tissue which includes the cell.

3. A method of claim 1 wherein the voltage is applied between the first electrode and the second electrode before the chemical agent is injected into the organism.

4. A method of claim 1 wherein the voltage is applied between the first electrode and the second electrode during injection of the chemical agent into the organism.

5. A method of claim 1 wherein the voltage is applied between the first electrode and the second electrode after injection of the chemical agent into the organism.

6. A method of claim 1 wherein the voltage applied between the first electrode and the second electrode includes at least one pulse.

7. A method of claim 1 wherein the chemical agent is injected into an interior conduit of the organism.

8. A method of claim 7 wherein the interior conduit is selected from the group consisting of a blood vessel, a lymph duct, a gastrointestinal tract and a urinary tract.

9. A method of claim 1 wherein the chemical agent is injected into a joint of the organism.

10. A method of claim 1 wherein the chemical agent is injected into an abdominal cavity of the organism.

11. A method of claim 1 wherein the chemical agent is selected from the group consisting of toxins, DNA, drugs, water and physiologic saline.

12. A method of claim 1 wherein the chemical agent includes an antimicrobial agent.

13. A method for treating at least one cell, in vivo, comprising the steps of:

a) directing a catheter into a blood vessel of an organism, said catheter including a first electrode, and an opening through which a chemical can be injected into the organism proximate to the cell to be treated;

b) placing a second electrode in a position where the cell and the opening of the catheter are between the first and second electrodes;

c) injecting the chemical into the organism through the catheter in an amount sufficient to treat the cell during electroporation of the cell; and

d) applying a voltage between the first and second electrodes in an amount sufficient to cause electroporation of at least a portion of the cell, whereby the chemical agent migrates across the cell membrane, thereby treating the cell.

14. A method of claim 13 wherein the blood vessel includes an artificial blood vessel.

15. A method of claim 13 wherein the point of chemical agent injection in the blood vessel allows the chemical agent to pass along the portion of the blood vessel wall which is electroporated after a period of time following injection of the chemical agent, and wherein the voltage applied between the first electrode and the second electrode includes at least one electrical pulse.

16. A method of claim 13 wherein the voltage is applied across the blood vessel wall while the chemical agent passes along the blood vessel wall.

17. A method for treating at least one cell, in vivo, comprising the steps of:

a) directing an endoscope into a blood vessel of an organism, said endoscope including a first electrode, and an opening through which a chemical can be injected into the organism proximate to the cell to be treated;

b) placing a second electrode in a position where the cell and the opening of the endoscope are between the first and second electrodes;

c) injecting the chemical into the organism through the endoscope in an amount sufficient to treat the cell during electroporation of the cell; and

d) applying a voltage between the first and second electrodes in an amount sufficient to cause electroporation of at least a portion of the cell, whereby the chemical agent migrates across the cell membrane, thereby treating the cell.

18. An apparatus for treating at least one cell, comprising:

a) a penetrator having a penetrating end, for penetration of an organism, and an opening through which a chemical agent can be injected into the organism proximate to the cell to be treated;

b) a first electrode at the penetrating end;

c) a second electrode located on the penetrator at a spaced interval from the first electrode wherein the opening is between the first and second electrodes; and

d) means connected to the first and second electrodes for applying a voltage between said electrodes in an amount sufficient to electroporate the cell, whereby said chemical agent in the organism migrates across the cell membrane and into the electroporated cell, thereby treating the cell.

19. An apparatus of claim 18 wherein the penetrator is a catheter.

20. An apparatus of claim 18 wherein the penetrator is an endoscope.

21. An apparatus of claim 18 wherein the surface area of the second electrode is larger than the surface area of the first electrode, whereby a substantial portion of the electroporation will occur at cells of the organism proximate to the first electrode.

22. An apparatus for treating at least one cell of an organism with a chemical agent, comprising:

a) a penetrator for penetration of a organism having a penetrating end;

b) a first electrode disposed at the penetrating end of the penetrator whereby the first electrode is disposed adjacent to the cell when the penetrator penetrates the organism;

c) a second electrode for applying a voltage between the first and second electrodes to cause electroporation of the cell;

d) a porous member for introducing the chemical agent into the organism, whereby disposing the porous member in the organism causes the chemical agent to migrate from the porous member to the cell for treatment of the cell during electroporation; and

e) means connected to the first and second electrodes for applying a voltage between said electrodes in an amount sufficient to electroporate the cell, whereby the chemical agent in the organism migrates across the cell membrane and into the electroporated cell, thereby treating the cell.

23. In a method for treating at least one cell with a chemical agent by electroporation which includes directing a chemical agent into the organism in an amount sufficient to treat the cell during electroporation of the cell:

The improvement comprising directing a penetrator into an organism, said penetrator including a first electrode, and an opening through which the chemical agent can be injected into the organism proximate to the cell, placing a second electrode in a position where said second electrode causes the cell and the opening of the penetrator are between the first and second electrodes, injecting the chemical agent into the organism through the penetrator in an amount sufficient to treat the cell during electroporation of the cell, and applying a voltage between the first and second electrodes in an amount sufficient to cause electroporation of at least a portion of the cell, whereby the chemical agent migrates across the cell membrane, thereby treating the cell.