Surgery – Means for introducing or removing material from body for... – Infrared – visible light – ultraviolet – x-ray or electrical...
Reexamination Certificate
1999-01-21
2001-03-27
Bockelman, Mark (Department: 3763)
Surgery
Means for introducing or removing material from body for...
Infrared, visible light, ultraviolet, x-ray or electrical...
C607S116000, C607S148000
Reexamination Certificate
active
06208893
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to the field of electroporation, and more specifically to the use of electroporation to introduce agents to a neoplastic cell to damage the cell.
BACKGROUND OF THE INVENTION
A cell has a natural resistance to the passage of molecules through its membranes into the cell cytoplasm. Scientists in the 1970's first discovered “clectroporation”, where electrical fields are used to create pores in cells without causing permanent damage to them. This discovery made possible the insertion of large molecules directly into cell cytoplasm. Electroporation was further developed to aid in the insertion of various molecules into cell cytoplasm by temporarily creating pores in the cells through which the molecules pass into the cell.
Electroporation has been used to implant materials into many different types of cells. Such cells, for example, include eggs, platelets, human cells, red blood cells, mammalian cells, plant protoplasts, plant pollen, liposomes, bacteria, fungi, yeast, and sperm. Further-more, electroporation has been used to implant a variety of different materials, referred to herein as “implant materials”, “implant molecules”, and “implant agents”. These materials have included DNA, genes, and various chemical agents.
Electroporation has been used in both in vitro and in vivo procedures to introduce foreign material into living cells. With in vitro applications, a sample of live cells is first mixed with the implant agent and placed between electrodes such as parallel plates. Then, the electrodes apply an electrical field to the cell/implant mixture.
With in vivo applications of electroporation, electrodes are provided in various configurations such as, for example, a caliper that grips the epidermis overlying a region of cells to be treated. Alternatively, needle-shaped electrodes may be inserted into the patient, to access more deeply located cells. In either case, after the implant agent is injected into the treatment region, the electrodes apply an electrical field to the region. Examples of systems that perform in vivo electroporation include the Electro Cell Manipulator ECM 600 product, and the Electro Square Porator T820, both made by and available from the BTX Division of Genetronics, Inc.
In the treatment of certain types of cancer with chemotherapeutic agents it is necessary to use a high enough dose of a drug to kill the cancer cells without killing an unacceptably high number of normal cells. If the chemotherapy drug could be inserted directly inside the cancer cells, this objective could be achieved. Some of the best anti-cancer drugs, for example, bleomycin, normally cannot penetrate the membranes of certain cancer cells effectively. However, electroporation makes it possible to insert the bleomycin into the cells.
In general, the treatment is carried out by infusing an anticancer drug directly into the tumor and applying an electric field to the tumor between one or more pairs of electrodes. The molecules of the drug are suspended in the interstitial fluid between and in and around the tumor cells. By electroporating the tumor cells, molecules of the drug adjacent to many of the cells are forced or drawn into the cell, subsequently killing the cancerous tumor cell. “Electrochemotherapy” is the therapeutic application of electroporation to deliver chemotherapeutic agents directly to tumor cells.
Known electroporation techniques (both in vitro and in vivo) function by applying a brief high voltage pulse to electrodes positioned around the treatment region. The electric field generated between the electrodes causes the cell membranes to temporarily become porous, whereupon molecules of the implant agent enter the cells. In known electroporation applications, this electric field comprises a single square wave pulse on the order of 1000 V/cm. of about 100 &mgr;s duration. Such a pulse may be generated, for example, in known applications of the Electro Square Porator T820, made by the BTX Division of Genetronics, Inc. Needle electrodes have been found to be very useful in the application of electroporation to many organs of the body and to tumors in the body.
An electric field may actually damage the electroporated cells in some cases. For example, an excessive electric field may damage the cells by creating permanent pores in the cell walls. In extreme cases, the electric field may completely destroy the cell. It is desirable that improved electroporation methods and apparatus with selectable needle electrode arrays be available.
SUMMARY OF THE INVENTION
The invention provides a therapeutic electroporation apparatus for the treatment of cells, particularly a neoplastic cell, in order to damage the cell.
A primary aspect of the invention includes an electrode template apparatus. Thief electrode template apparatus includes a primary support member having opposite surfaces, a plurality of bores extending through the support member and through the opposite surfaces, a plurality of conductors on the support member separately connected to at least one of the plurality of bores, a plurality of electrodes selectively extendable through the plurality of bores so that each conductor is connected to at least one electrode, and a means for connecting the conductors to a power supply. The electrode template apparatus is utilized to apply a high voltage electric field to the cell in order to introduce a therapeutic agent into the cell.
In accordance with another aspect of the invention, the apparatus includes a primary support member having opposite parallel surfaces, a plurality of bores arranged in a rectangular array and extending through the support member and through the opposite surfaces, a plurality of conductors on the support member separately connected to at least one of the plurality of bores, a plurality of needle electrodes mounted in the plurality of bores so that each conductor is connected to at least one electrode, wherein at least one of the needle electrodes has a tubular configuration for injection of the agent into the tissue; and connectors for connecting the conductors to a power supply. The tissue is contacted with the agent; and a pulse of high amplitude electric signals is applied to the cell, for electroporation of the cell with the agent.
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Baker & Maxham
Bockelman Mark
Genetronics Inc.
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