WO2004030760A2 - Apparatus for treating a tumor by an electric field - Google Patents

Abstract

An apparatus is provided for selectively destroying dividing cells in living tissue formed of dividing cells and non-dividing cells. The dividing cells contain polarizable intracellular members and during late anaphase or telophase, the dividing cells are connected to one another by a cleavage furrow. The apparatus includes insulated electrodes to be coupled to a generator for subjecting the living tissue to electric field conditions sufficient to cause movement of the polarizable intracellular members toward the cleavage furrow in response to a non-homogeneous electric field being induced in the dividing cells. The movement of the polarizable intracellular intracellular members towards the cleavage furrow causes the breakdown thereof which adversely impacts the multiplication of the dividing cells. Preferably, an intervening member is disposed between each insulated electrode and the skin surface and each intervening member includes a conductive 'floating' plate that protects against the effects on the patient from a breakdown in the insulation of the electrode.

Description

APPARATUS FOR TREATING A TUMOR OR THE LIKE AND ARTICLES INCORPORATING THE APPARATUS

FOR TREATMENT OF THE TUMOR

Cross-Reference Related Applications

This application claims the benefit of U.S. patent application No.

10/315,576, filed December 10, 2002, which is a continuation-in-part application

of U.S. patent application serial No. 10/285,313, filed October 31, 2002, which is

a continuation-in-part application of U.S. patent application serial No. 10/263,329,

filed October 2, 2002, which are hereby incorporated by reference in their

entirety.

Technical Field

This invention concerns selective destruction of rapidly dividing

cells in a localized area, and more particularly, to an apparatus and method for

selectively destroying dividing cells by applying an electric field having certain prescribed characteristics using an apparatus that is configured to be

complimentary to a specific body part.

Background

All living organisms proliferate by cell division, including cell

cultures, microorganisms (such as bacteria, mycoplasma, yeast, protozoa, and

other single-celled organisms), fungi, algae, plant cells, etc. Dividing cells of

organisms can be destroyed, or their proliferation controlled, by methods that are

based on the sensitivity of the dividing cells of these organisms to certain agents.

For example, certain antibiotics stop the multiplication process of bacteria.

The process of eukaryotic cell division is called "mitosis", which

involves nice distinct phases (see Darnell et al, Molecular Cell Biology, New

York: Scientific American Books, 1986, p. 149). During interphase, the cell

replicates chromosomal DNA, which begins condensing in early prophase. At

this point, centrioles (each cell contains 2) begin moving towards opposite poles

of the cell. In middle prophase, each chromosome is composed of duplicate

chromatids. Microtubular spindles radiate from regions adjacent to the

centrioles, which are closer to their poles. By late prophase, the centrioles have reached the poles, and some spindle fibers extend to the center of the cell, while

others extend from the poles to the chromatids. The cells then move into

metaphase, when the chromosomes move toward the equator of the cell and align

in the equatorial plane. Next is early anaphase, during which time daughter

chromatids separate from each other at the equator by moving along the spindle

fibers toward a centromere at opposite poles. The cell begins to elongate along

the axis of the pole; the pole-to-pole spindles also elongate. Late anaphase

occurs when the daughter chromosomes (as they are not called) each reach their

respective opposite poles. At this point, cytokinesis begins as the cleavage

furrow begins to form at the equator of the cell. In other words, late anaphase is

the point at which pinching the cell membrane begins. During telophase,

cytokinesis is nearly complete and spindles disappear. Only a relatively narrow

membrane connection joins the two cytoplasms. Finally, the membranes separate

fully, cytokinesis is complete and the cell returns to interphase.

In meisosis, the cell undergoes a second division, involving

separation of sister chromosomes to opposite poles of the cell along spindle

fibers, followed by formation of a cleavage furrow and cell division. However,

this division is not preceded by chromosome replication, yielding a haploid germ

cell. Bacteria also divide by chromosome replication, followed by cell

separation. However, since the daughter chromosomes separate by attachment to

membrane components; there is no visible apparatus that contributes to cell

division as in eukaryotic cells.

It is well known that tumors, particularly malignant or cancerous

tumors, grow uncontrollably compared to normal tissue. Such expedited growth

enables tumors to occupy an ever-increasing space and to damage or destroy

tissue adjacent thereto. Furthermore, certain cancers are characterized by an

ability to transmit cancerous "seeds", including single cells or small cell clusters

(metastasises), to new locations where the messastatic cancer cells grow into

additional tumors.

The rapid growth of tumors, in general, and malignant tumors in

particular, as described above, is the result of relatively frequent cell division or

multiplication of these cells compared to normal tissue cells. The distinguishably

frequent cell division of cancer cells is the basis for the effectiveness of existing

cancer treatments, e.g., irradiation therapy and the use of various chemo¬

therapeutic agents. Such treatments are based on the fact that cells undergoing

division are more sensitive to radiation and chemo-therapeutic agents than non- dividing cells. Because tumors cells divide much more frequently than normal

cells, it is possible, to a certain extent, to selectively damage or destroy tumor

cells by radiation therapy and/or chemotherapy. The actual sensitivity of cells to

radiation, therapeutic agents, etc., is also dependent on specific characteristics of

different types of normal or malignant cell types. Thus, unfortunately, the

sensitivity of tumor cells is not sufficiently higher than that many types of normal

tissues. This diminishes the ability to distinguish between tumor cells and

normal cells, and therefore, existing cancer treatments typically cause significant

damage to normal tissues, thus limiting the therapeutic effectiveness of such

treatments. Furthermore, the inevitable damage to other tissue renders treatments

very traumatic to the patients and, often, patients are unable to recover from a

seemingly successful treatment. Also, certain types of tumors are not sensitive at

all to existing methods of treatment.

There are also other methods for destroying cells that do not rely

on radiation therapy or chemotherapy alone. For example, ultrasonic and

electrical methods for destroying tumor cells can be used in addition to or instead

of conventional treatments. Electric fields and currents have been used for

medical purposes for many years. The most common is the generation of electric

currents in a human or animal body by application of an electric field by means of a pair of conductive electrodes between which a potential difference is

maintained. These electric currents are used either to exert their specific effects,

i.e., to stimulate excitable tissue, or to generate heat by flowing in the body since

it acts as a resistor. Examples of the first type of application include the

following: cardiac defibrillators, peripheral nerve and muscle stimulators, brain

stimulators, etc. Currents are used for heating, for example, in devices for tumor

ablation, ablation of malfunctioning cardiac or brain tissue, cauterization,

relaxation of muscle rheumatic pain and other pain, etc.

Another use of electric fields for medical purposes involves the

utilization of high frequency oscillating fields transmitted from a source that

emits an electric wave, such as an RF wave or a microwave source that is

directed at the part of the body that is of interest (i.e., target). In these instances,

there is no electric energy conduction between the source and the body; but

rather, the energy is transmitted to the body by radiation or induction. More

specifically, the electric energy generated by the source reaches the vicinity of the

body via a conductor and is transmitted from it through air or some other electric

insulating material to the human body. In a conventional electrical method, electrical current is delivered

to a region of the target tissue using electrodes that are placed in contact with the

body of the patient. The applied electrical current destroys substantially all cells

in the vicinity of the target tissue. Thus, this type of electrical method does not

discriminate between different types of cells within the target tissue and results in

the destruction of both tumor cells and normal cells.

Electric fields that can be used in medical applications can thus be

separated generally into two different modes. In the first mode, the electric fields

are applied to the body or tissues by means of conducting electrodes. These

electric fields can be separated into two types, namely (1) steady fields or fields

that change at relatively slow rates, and alternating fields of low frequencies that

induce corresponding electric currents in the body or tissues, and (2) high

frequency alternating fields (above 1MHz) applied to the body by means of the

conducting electrodes. In the second mode, the electric fields are high frequency

alternating fields applied to the body by means of insulated electrodes.

The first type of electric field is used, for example, to stimulate

nerves and muscles, pace the heart, etc. In fact, such fields are used in nature to

propagate signals in nerve and muscle fibers, central nervous system (CNS), heart, etc. The recording of such natural fields is the basis for the ECG, EEG,

EMG, ERG, etc. The field strength in these applications, assuming a medium of

homogenous electric properties, is simply the voltage applied to the

stimulating/recording electrodes divided by the distance between them. These

currents can be calculated by Ohm's law and can have dangerous stimulatory

effects on the heart and CNS and can result in potentially harmful ion

concentration changes. Also, if the currents are strong enough, they can cause

excessive heating in the tissues. This heating can be calculated by the power

dissipated in the tissue (the product of the voltage and the current).

When such electric fields and currents are alternating, their

stimulatory power, on nerve, muscle, etc., is an inverse function of the frequency.

At frequencies above 1-10 KHz, the stimulation power of the fields approaches

zero. This limitation is due to the fact that excitation induced by electric

stimulation is normally mediated by membrane potential changes, the rate of

which is limited by the RC properties (time constants on the order of 1 ms) of the

membrane.

Regardless of the frequency, when such current inducing fields are

applied, they are associated with harmful side effects caused by currents. For example, one negative effect is the changes in ionic concentration in the various

"compartments" within the system, and the harmful products of the electrolysis

taking place at the electrodes, or the medium in which the tissues are imbedded.

The changes in ion concentrations occur whenever the system includes two or

more compartments between which the organism maintains ion concentration

differences. For example, for most tissues, [Ca⁺⁺] in the extracellular fluid is

about 2 x 10^"3 M, while in the cytoplasm of typical cells its concentration can be

as low as 10^"7 M. A current induced in such a system by a pair of electrodes,

flows in part from the extracellular fluid into the cells and out again into the

extracellular medium. About 2% of the current flowing into the cells is carried

by the Ca⁺⁺ ions. In contrast, because the concentration of intracellular Ca⁺⁺ is

much smaller, only a negligible fraction of the currents that exits the cells is

carried by these ions. Thus, Ca⁺⁺ ions accumulate in the cells such that their

concentrations in the cells increases, while the concentration in the extracellular

compartment may decrease. These effects are observed for both DC and

alternating currents (AC). The rate of accumulation of the ions depends on the

current intensity ion mobilities, membrane ion conductance, etc. An increase in

[Ca⁺⁺] is harmful to most cells and if sufficiently high will lead to the destruction

of the cells. Similar considerations apply to other ions. In view of the above observations, long term current application to living organisms or tissues can

result in significant damage. Another major problem that is associated with such

electric fields, is due to the electrolysis process that takes place at the electrode

surfaces. Here charges are transferred between the metal (electrons) and the

electrolytic solution (ions) such that charged active radicals are formed. These

can cause significant damage to organic molecules, especially macromolecules

and thus damage the living cells and tissues.

In contrast, when high frequency electric fields, above 1 MHz and

usually in practice in the range of GHz, are induced in tissues by means of

insulated electrodes, the situation is quite different. These type of fields generate

only capacitive or displacement currents, rather than the conventional charge

conducting currents. Under the effect of this type of field, living tissues behave

mostly according to their dielectric properties rather than their electric conductive

properties. Therefore, the dominant field effect is that due to dielectric losses and

heating. Thus, it is widely accepted that in practice, the meaningful effects of

such fields on living organisms, are only those due to their heating effects, i.e.,

due to dielectric losses. In U.S. Patent No. 6,043,066 ('066) to Mangano, a method and

device are presented which enable discrete objects having a conducting inner

core, surrounded by a dielectric membrane to be selectively inactivated by

electric fields via irreversible breakdown of their dielectric membrane. One

potential application for this is in the selection and purging of certain biological

cells in a suspension. According to the '066 patent, an electric field is applied for

targeting selected cells to cause breakdown of the dielectric membranes of these

tumor cells, while purportedly not adversely affecting other desired

subpopulations of cells. The cells are selected on the basis of intrinsic or induced

differences in a characteristic electroporation threshold. The differences in this

threshold can depend upon a number of parameters, including the difference in

cell size.

The method of the '066 patent is therefore based on the

assumption that the electroporation threshold of tumor cells is sufficiently

distinguishable from that of normal cells because of differences in cell size and

differences in the dielectric properties of the cell membranes. Based upon this

assumption, the larger size of many types of tumor cells makes these cells more

susceptible to electroporation and thus, it may be possible to selectively damage

only the larger tumor cell membranes by applying an appropriate electric field. One disadvantage of this method is that the ability to discriminate is highly

dependent upon cell type, for example, the size difference between normal cells

and tumor cells is significant only in certain types of cells. Another drawback of

this method is that the voltages which are applied can damage some of the normal

cells and may not damage all of the tumor cells because the differences in size

and membrane dielectric properties are largely statistical and the actual cell

geometries and dielectric properties can vary significantly.

What is needed in the art and has heretofore not been available is

an apparatus for destroying dividing cells, wherein the apparatus better

discriminates between dividing cells, including single-celled organisms, and non-

dividing cells and is capable of selectively destroying the dividing cells or

organisms with substantially no affect on the non-dividing cells or organisms and

which can be configured to applied to a specific body part, such as an extremity

and thus lends itself to being incorporated into an article of clothing.

Summary

An apparatus for use in a number of different applications for

selectively destroying cells undergoing growth and division is provided. This includes, cell, particularly tumor cells, in living tissue and single-celled

organisms. The apparatus can be incorporated into a number of different

configurations that are specifically designed to be effective for specific body

parts so that the apparatus distinctly targets a localized area to eliminate or

control the growth of such living tissue or organisms. For example and as will be

described in greater detail hereinafter, the apparatus is particularly capable of

being incorporated into a piece of clothing that is worn over the tumor area. One

of the configurations of the apparatus is in the form of a hat, cap or other type of

structure to be fitted over a person's head for treating intra-cranial tumors,

external scalp lesions or other lesions. In another configuration, the apparatus is

in the form of a modified bra or the like to be fitted over breasts for treating

breast cancer or other type of tumor condition. In addition, the apparatus can be

incorporated into clothing that is to be worn over other body parts, such as

testicles, a hand, leg, arm, neck, etc., for treating a localized tumor in one of these

locations (body parts). For example, a high standing collar member or necklace

type structure can be used to treat thyroid, parathyroid, laryngeal lesions, etc. In

this embodiment, the apparatus (either completely or partially) is disposed within

clothing that is fit around the neck for treating these conditions. In another aspect,

localized treatment is provided by the apparatus when it is in the form of an internal member (e.g., a probe or catheter) that is inserted into the body through a

natural pathway, such as the urethra, vagina, etc., or the member can penetrate

the skin to and other tissues to reach an internal target.

A major use of the present apparatus is in the treatment of tumors

by selective destruction of tumor cells with substantially no affect on normal

tissue cells, and thus, the exemplary apparatus is described below in the context

of selective destruction of tumor cells. It should be appreciated however, that for

purpose of the following description, the term "cell" may also refer to a single-

celled organism (eubacteria, bacteria, yeast, protozoa), multi-celled organisms

(fungi, algae, mold), and plants as or parts thereof that are not normally classified

as "cells". The exemplary apparatus enables selective destruction of cells

undergoing division in a way that is more effective and more accurate (e.g., more

adaptable to be aimed at specific targets) than existing methods. Further, the

present apparatus causes minimal damage, if any, to normal tissue and, thus,

reduces or eliminates many side-effects associated with existing selective

destruction methods, such as radiation therapy and chemotherapy. The selective

destruction of dividing cells using the present apparatus does not depend on the

sensitivity of the cells to chemical agents or radiation. Instead, the selective

destruction of dividing cells is based on distinguishable geometrical characteristics of cells undergoing division, in comparison to non-dividing cells,

regardless of the cell geometry of the type of cells being treated.

According to one exemplary embodiment, cell geometry-

dependent selective destruction of living tissue is performed by inducing a non-

homogenous electric field in the cells using an electronic apparatus.

It has been observed by the present inventor that, while different

cells in their non-dividing state may have different shapes, e.g., spherical,

ellipsoidal, cylindrical, "pancake-like", etc., the division process of practically all

cells is characterized by development of a "cleavage furrow" in late anaphase and

telophase. This cleavage furrow is a slow

cell membrane

(between the two sets of daughter chromosomes) which appears microscopically

as a growing cleft (e.g., a groove or notch) that gradually separates the cell into

two new cells. During the division process, there is a transient period (telophase)

during which the cell structure is basically that of two sub-cells interconnected by

a narrow "bridge" formed of the cell material. The division process is completed

when the "bridge" between the two sub-cells is broken. The selective destruction

of tumor cells using the present electronic apparatus utilizes this unique

geometrical feature of dividing cells. When a cell or a group of cells are under natural conditions or

environment, i.e., part of a living tissue, they are disposed surrounded by a

conductive environment consisting mostly of an electrolytic inter-cellular fluid

and other cells that are composed mostly of an electrolytic intra-cellular liquid.

When an electric field is induced in the living tissue, by applying an electric

potential across the tissue, an electric field is formed in the tissue and the specific

distribution and configuration of the electric field lines defines the direction of

charge displacement, or paths of electric currents in the tissue, if currents are in

fact induced in the tissue. The distribution and configuration of the electric field

is dependent on various parameters of the tissue, including the geometry and the

electric properties of the different tissue components, and the relative

conductivities, capacities and dielectric constants (that may be frequency

dependent) of the tissue components.

The electric current flow pattern for cells undergoing division is

very different and unique as compared to non-dividing cells. Such cells including

first and second sub-cells, namely an "original" cell and a newly formed cell, that

are connected by a cytoplasm "bridge" or "neck". The currents penetrate the first

sub-cell through part of the membrane ("the current source pole"); however, they

do not exit the first sub-cell through a portion of its membrane closer to the opposite pole ("the current sink pole"). Instead, the lines of current flow

converge at the neck or cytoplasm bridge, whereby the density of the current flow

lines is greatly increased. A corresponding, "mirror image", process that takes

place in the second sub-cell, whereby the current flow lines diverge to a lower

density configuration as they depart from the bridge, and finally exit the second

sub-cell from a part of its membrane closes to the current sink.

When a polarizable object is placed in a non-uniform converging

or diverging field, electric forces act on it and pull it towards the higher density

electric field lines. In the case of dividing cell, electric forces are exerted in the

direction of the cytoplasm bridge between the two cells. Since all intercellular

organelles and macromolecules are polarizable, they are all force towards the

bridge between the two cells. The field polarity is irrelevant to the direction of

the force and, therefore, an alternating electric having specific properties can be

used to produce substantially the same effect. It will also be appreciated that the

concentrated and inhomogeneous electric field present in or near the bridge or

neck portion in itself exerts strong forces on charges and natural dipoles and can

lead to the disruption of structures associated with these members.

The movement of the cellular organelles towards the bridge

disrupts the cell structure and results in increased pressure in the vicinity of the connecting bridge membrane. This pressure of the organelles on the bridge

membrane is expected to break the bridge membrane and, thus, it is expected that

the dividing cell will "explode" in response to this pressure. The ability to break

the membrane and disrupt other cell structures can be enhanced by applying a

pulsating alternating electric field that has a frequency from about 50KHz to

about 500KHz. When this type of electric field is applied to the tissue, the forces

exerted on the intercellular organelles have a "hammering" effect, whereby force

pulses (or beats) are applied to the organelles numerous times per second,

enhancing the movement of organelles of different sizes and masses towards the

bridge (or neck) portion from both of the sub-cells, thereby increasing the

probability of breaking the cell membrane at the bridge portion. The forces

exerted on the intracellular organelles also affect the organelles themselves and

may collapse or break the organelles.

According to one exemplary embodiment, the apparatus for

applying the electric field is an electronic apparatus that generates the desired

electric signals in the shape of waveforms or trains of pulses. The electronic

apparatus includes a generator that generates an alternating voltage waveform at

frequencies in the range from about 50KHz to about 500KHz. The generator is

operatively connected to conductive leads which are connected at their other ends to insulated conductors/electrodes (also referred to as isolects) that are activated

by the generated waveforms. The insulated electrodes consist of a conductor in

contact with a dielectric (insulating layer) that is in contact with the conductive

tissue, thus forming a capacitor. The electric fields that are generated by the

present apparatus can be applied in several different modes depending upon the

precise treatment application.

In one exemplary embodiment, the electric fields are applied by

external insulated electrodes which are incorporated into an article of clothing

and which are constructed so that the applied electric fields are of a local type

that target a specific, localized area of tissue (e.g., a tumor). This embodiment is

designed to treat tumors and lesions that are at or below the skin surface by

wearing the article of clothing over the target tissue so that the electric fields

generated by the insulated electrodes are directed at the tumors (lesions, etc.).

According to another embodiment, the apparatus is used in an

internal type application in that the insulated electrodes are in the form of a probe

or catheter etc., that enter the body through natural pathways, such as the urethra

or vagina, or are configured to penetrate living tissue, until the insulated

electrodes are positioned near the internal target area (e.g., an internal tumor). Thus, the present apparatus utilizes electric fields that fall into a

special intermediate category relative to previous high and low frequency

applications in that the present electric fields are bio-effective fields that have no

meaningful stimulatory effects and no thermal effects. Advantageously, when

non-dividing cells are subjected to these electric fields, there is no effect on the

cells; however, the situation is much different when dividing cells are subjected

to the present electric fields. Thus, the present electronic apparatus and the

generated electric fields target dividing cells, such as tumors or the like, and do

not target non-dividing cells that is found around in healthy tissue surrounding

the target area. Furthermore, since the present apparatus utilizes insulated

electrodes, the above mentioned negative effects, obtained when conductive

electrodes are used, i.e., ion concentration changes in the cells and the formation

of harmful agents by electrolysis, do not occur with the present apparatus. This is

because, in general, no actual transfer of charges takes place between the

electrodes and the medium, and there is no charge flow in the medium where the

currents are capacitive.

It should be appreciated that the present electronic apparatus can

also be used in applications other than treatment of tumors in the living body. In

fact, the selective destruction utilizing the present apparatus can be used in conjunction with any organism that proliferates division and multiplication, for

example, tissue cultures, microorganisms, such as bacteria, mycoplasma,

protozoa, fungi, algae, plant cells, etc. Such organisms divide by the formation

of a groove or cleft as described above. As the groove or cleft deepens, a narrow

bridge is formed between the two parts of the organism, similar to the bridge

formed between the sub-cells of dividing animal cells. Since such organisms are

covered by a membrane having a relatively low electric conductivity, similar to

an animal cell membrane described above, the electric field lines in a dividing

organism converge at the bridge connecting the two parts of the dividing

organism. The converging field lines result in electric forces that displace

polarizable elements and charges within the dividing organism.

The above, and other objects, features and advantages of the

present apparatus will become apparent from the following description read in

conjunction with the accompanying drawings, in which like reference numerals

designate the same elements.

Brief Description of the Drawing Figures

Figs. 1A-1E are simplified, schematic, cross-sectional, illustrations

of various stages of a cell division process; Figs. 2 A and 2B are schematic illustrations of a non-dividing cell

being subjected to an electric field;

Figs. 3 A, 3B and 3C are schematic illustrations of a dividing cell

being subjected to an electric field according to one exemplary embodiment,

resulting in destruction of the cell (Fig. 3C) in accordance with one exemplary

embodiment;

Fig. 4 is a schematic illustration of a dividing cell at one stage

being subject to an electric field;

Fig. 5 is a schematic block diagram of an apparatus for applying

an electric according to one exemplary embodiment for selectively destroying

cells;

Fig. 6 is a simplified schematic diagram of an equivalent electric

circuit of insulated electrodes of the apparatus of Fig. 5;

Fig. 7 is a cross-sectional illustration of a skin patch incorporating

the apparatus of Fig. 5 and for placement on a skin surface for treating a tumor or

the like;

Fig. 8 is a cross-sectional illustration of the insulated electrodes

implanted within the body for treating a tumor or the like; Fig. 9 is a cross-sectional illustration of the insulated electrodes

implanted within the body for treating a tumor or the like;

Figs. 10A-10D are cross-sectional illustrations of various

constructions of the insulated electrodes of the apparatus of Fig. 5;

Fig. 11 is a front elevational view in partial cross-section of two

insulated electrodes being arranged about a human torso for treatment of a tumor

container within the body, e.g., a tumor associated with lung cancer;

Figs. 12A-12C are cross-sectional illustrations of various insulated

electrodes with and without protective members formed as a part of the

construction thereof;

Fig. 13 is a schematic diagram of insulated electrodes that are

arranged for focusing the electric field at a desired target while leaving other

areas in low field density (i.e., protected areas);

Fig. 14 is a cross-sectional view of insulated electrodes

incorporated into a hat according to a first embodiment for placement on a head

for treating an intra-cranial tumor or the like;

Fig. 15 is a partial section of a hat according to an exemplary

embodiment having a recessed section for receiving one or more insulated

electrodes; Fig. 16 is a cross-sectional view of the hat of Fig. 15 placed on a

head and illustrating a biasing mechanism for applying a force to the insulated

electrode to ensure the insulated electrode remains in contact against the head;

Fig. 17 is a cross-sectional top view of an article of clothing

having the insulated electrodes incorporated therein for treating a tumor or the

like;

Fig. 18 is a cross-sectional view of a section of the article of

clothing of Fig. 17 illustrating a biasing mechanism for biasing the insulated

electrode in direction to ensure the insulated electrode is placed proximate to a

skin surface where treatment is desired;

Fig. 19 is a cross-sectional view of a probe according to one

embodiment for being disposed internally within the body for treating a tumor or

the like;

Fig. 20 is an elevational view of an unwrapped collar according to

one exemplary embodiment for placement around a neck for treating a tumor or

the like in this area when the collar is wrapped around the neck;

Fig. 21 is a cross-sectional view of two insulated electrodes with

conductive gel members being arranged about a body, with the electric field lines

being shown; Fig. 22 is a cross-sectional view of the arrangement of Fig. 21

illustrating a point of insulation breakdown in one insulated electrode;

Fig. 23 is a cross-sectional view of an arrangement of at least two

insulated electrodes with conductive gel members being arranged about a body

for treatment of a tumor or the like, wherein each conductive gel member has a

feature for minimizing the effects of an insulation breakdown in the insulated

electrode;

Fig. 24 is a cross-sectional view of another arrangement of at least

two insulated electrodes with conductive gel members being arranged about a

body for treatment of a tumor or the like, wherein a conductive member is

disposed within the body near the tumor to create a region of increased field

density;

Fig. 25 is a cross-sectional view of an arrangement of two

insulated electrodes of varying sizes disposed relative to a body; and

Fig. 26 is a cross-sectional view of an arrangement of at least two

insulated electrodes with conductive gel members being arranged about a body

for treatment of a tumor or the like, wherein each conductive gel member has a

feature for minimizing the effects of an insulation breakdown in the insulated

electrode. Detailed Description of Preferred Embodiments

Reference is made to Figs. 1 A- IE which schematically illustrate

various stages of a cell division process. Fig. 1A illustrates a cell 10 at its normal

geometry, which can be generally spherical (as illustrated in the drawings),

ellipsoidal, cylindrical, "pancake-like" or any other cell geometry, as is known in

the art. Figs. IB- ID illustrate cell 10 during different stages of its division

process, which results in the formation of two new cells 18 and 20, shown in Fig.

IE.

As shown in Figs. IB-ID, the division process of cell 10 is

characterized by a slowly growing cleft 12 which gradually separates cell 10 into

two units, namely sub-cells 14 and 16, which eventually evolve into new cells 18

and 20 (Fig. IE). A shown specifically in Fig. ID, the division process is

characterized by a transient period during which the structure of cell 10 is

basically that of the two sub-cells 14 and 16 interconnected by a narrow "bridge"

22 containing cell material (cytoplasm surrounded by cell membrane).

Reference is now made to Figs. 2 A and 2B, which schematically

illustrate non-dividing cell 10 being subjected to an electric field produced by applying an alternating electric potential, at a relatively low frequency and at a

relatively high frequency, respectively. Cell 10 includes intracellular organelles,

e.g., a nucleus 30. Alternating electric potential is applied across electrodes 28

and 32 that can be attached externally to a patient at a predetermined region, e.g.,

in the vicinity of the tumor being treated. When cell 10 is under natural

conditions, i.e., part of a living tissue, it is disposed in a conductive environment

(hereinafter referred to as a "volume conductor") consisting mostly of electrolytic

inter-cellular liquid. When an electric potential is applied across electrodes 28

and 32, some of the field lines of the resultant electric field (or the current

induced in the tissue in response to the electric field) penetrate the cell 10, while

the rest of the field lines (or induced current) flow in the surrounding medium.

The specific distribution of the electric field lines, which is substantially

consistent with the direction of current flow in this instance, depends on the

geometry and the electric properties of the system components, e.g., the relative

conductivities and dielectric constants of the system components, that can be

frequency dependent. For low frequencies, e.g., frequencies lower than lOKHz,

the conductance properties of the components completely dominate the current

flow and the field distribution, and the field distribution is generally as depicted

in Fig. 2A. At higher frequencies, e.g., at frequencies of between lOKHz and 1MHz, the dielectric properties of the components becomes more significant and

eventually dominate the field distribution, resulting in field distribution lines as

depicted generally in Fig. 2B.

For constant (i.e., DC) electric fields or relatively low frequency

alternating electric fields, for example, frequencies under lOKHz, the dielectric

properties of the various components are not significant in determining and

computing the field distribution. Therefore, as a first approximation, with regard

to the electric field distribution, the system can be reasonably represented by the

relative impedances of its various components. Using this approximation, the

intercellular (i.e., extracellular) fluid and the intracellular fluid each has a

relatively low impedance, while the cell membrane 11 has a relatively high

impedance. Thus, under low frequency conditions, only a fraction of the electric

field lines (or currents induced by the electric field) penetrate membrane 11 of the

cell 10. At relatively high frequencies (e.g., lOKHz - 1MHz), in contrast, the

impedance of membrane 11 relative to the intercellular and intracellular fluids

decreases, and thus, the fraction of currents penetrating the cells increases

significantly. It should be noted that at very high frequencies, i.e., above 1MHz,

the membrane capacitance can short the membrane resistance and, therefore, the

total membrane resistance can become negligible. In any of the embodiments described above, the electric field lines

(or induced currents) penetrate cell 10 from a portion of the membrane 11 closest

to one of the electrodes generating the current, e.g., closest to positive electrode

28 (also referred to herein as "source"). The current flow pattern across cell 10 is

generally uniform because, under the above approximation, the field induced

inside the cell is substantially homogeneous. The currents exit cell 10 through a

portion of membrane 11 closest to the opposite electrode, e.g., negative electrode

32 (also referred to herein as "sink").

The distinction between field lines and current flow can depend on

a number of factors, for example, on the frequency of the applied electric

potential and on whether electrodes 28 and 32 are electrically insulated. For

insulated electrodes applying a DC or low frequency alternating voltage, there is

practically no current flow along the lines of the electric field. At higher

frequencies, the displacement currents are induced in the tissue due to charging

and discharging of the electrode insulation and the cell membranes (which act as

capacitors to a certain extent), and such currents follow the lines of the electric

field. Fields generated by non-insulated electrodes, in contrast, always generate

some form of current flow, specifically, DC or low frequency alternating fields

generate conductive current flow along the field lines, and high frequency alternating fields generate both conduction and displacement currents along the

field lines. It should be appreciated, however, that movement of polarizable

intracellular organelles according to the present invention (as described below) is

not dependent on actual flow of current and, therefore, both insulated and non-

insulated electrodes can be used efficiently. Several advantages of insulated

electrodes are that they have lower power consumption and cause less heating of

the treated regions.

According to one exemplary embodiment of the present invention,

the electric fields that are used are alternating fields having frequencies that are in

the range from about 50KHz to about 500KHz, and preferably from about

lOOKHz to about 300KHz. For ease of discussion, these type of electric fields

are also referred to below as "TC fields", which is an abbreviation of "Tumor

Curing electric fields", since these electric fields fall into an intermediate

category (between high and low frequency ranges) that have bio-effective field

properties while having no meaningful stimulatory and thermal effects. These

frequencies are sufficiently low so that the system behavior is determined by the

system's Ohmic (conductive) properties but sufficiently high enough not to have

any stimulation effect on excitable tissues. Such a system consists of two types

of elements, namely, the intercellular, or extracellular fluid, or medium and the individual cells. The intercellular fluid is mostly an electrolyte with a specific

resistance of about 40-100 Ohm*cm. As mentioned above, the cells are

characterized by three elements, namely (1) a thin, highly electric resistive

membrane that coats the cell; (2) internal cytoplasm that is mostly an electrolyte

that contains numerous macromolecules and micro-organelles, including the

nucleus; and (3) membranes, similar in their electric properties to the cell

membrane, cover the micro-organelles.

When this type of system is subjected to the present TC fields

(e.g., alternating electric fields in the frequency range of lOOKHz - 300KHz)

most of the lines of the electric field and currents tend away from the cells

because of the high resistive cell membrane and therefore the lines remain in the

extracellular conductive medium. In the above recited frequency range, the

actual fraction of electric field or currents that penetrates the cells is a strong

function of the frequency.

Fig. 2 schematically depicts the resulting field distribution in the

system. As illustrated, the lines of force, which also depict the lines of potential

current flow across the cell volume mostly in parallel with the undistorted lines of

force (the main direction of the electric field). In other words, the field inside the cells is mostly homogeneous. In practice, the fraction of the field or current that

penetrates the cells is determined by the cell membrane impedance value relative

to that of the extracellular fluid. Since the equivalent electric circuit of the cell

membrane is that of a resistor and capacitor in parallel, the impedance is a

function of the frequency. The higher the frequency, the lower the impedance,

the larger the fraction of penetrating current and the smaller the field distortion

(Rotshenker S. & Y. Palti, Changes in fraction of current penetrating an axon as a

function of duration of stimulating pulse, J. Theor. Biol. 41; 401-407 (1973).

As previously mentioned, when cells are subjected to relatively

weak electric fields and currents that alternate at high frequencies, such as the

present TC fields having a frequency in the range of 50KHz - 500KHz, they have

no effect on the non-dividing cells. While the present TC fields have no

detectable effect on such systems, the situation becomes different in the presence

of dividing cells.

Reference is now made to Figs. 3A-3C which schematically

illustrate the electric current flow pattern in cell 10 during its division process,

under the influence of alternating fields (TC fields) in the frequency range from

about lOOKHz to about 300KHz in accordance with one exemplary embodiment. The field lines or induced currents penetrate cell 10 through a part of the

membrane of sub-cell 16 closer to electrode 28. However, they do not exit

through the cytoplasm bridge 22 that connects sub-cell 16 with the newly formed

yet still attached sub-cell 14, or through a part of the membrane in the vicinity of

the bridge 22. Instead, the electric field or current flow lines —that are relatively

widely separated in sub-cell 16— converge as they approach bridge 22 (also

referred to as "neck" 22) and, thus, the current/field line density within neck 22 is

increased dramatically. A "mirror image" process takes place in sub-cell 14,

whereby the converging field lines in bridge 22 diverge as they approach the exit

region of sub-cell 14.

It should be appreciated by persons skilled in the art that

homogeneous electric fields do not exert a force on electrically neutral objects,

i.e., objects having substantially zero net charge, although such objects can

become polarized. However, under a non-uniform, converging electric field, as

shown in Figs. 3A-3C, electric forces are exerted on polarized objects, moving

them in the direction of the higher density electric field lines. It will be

appreciated that the concentrated electric field that is present in the neck or

bridge area in itself exerts strong forces on charges and natural dipoles and can

disrupt structures that are associated therewith. One will understand that similar net forces act on charges in an alternating field, again in the direction of the field

of higher intensity.

In the configuration of Figs. 3 A and 3B, the direction of

movement of polarized and charged objects is towards the higher density electric

field lines, i.e., towards the cytoplasm bridge 22 between sub-cells 14 and 16. It

is known in the art that all intracellular organelles, for example, nuclei 24 and 26

of sub-cells 14 and 16, respectively, are polarizable and, thus, such intracellular

organelles are electrically forced in the direction of the bridge 22. Since the

movement is always from lower density currents to the higher density currents,

regardless of the field polarity, the forces applied by the alternating electric field

to organelles, such as nuclei 24 and 26, are always in the direction of bridge 22.

A comprehensive description of such forces and the resulting movement of

macromolecules of intracellular organelles, a phenomenon referred to as

"dielectrophoresis" is described extensively in literature, e.g., in C.L. Asbury &

G. van den Engh, Biophys. J. 74, 1024-1030, 1998, the disclosure of which is

hereby incorporated by reference in its entirety.

The movement of the organelles 24 and 26 towards the bridge 22

disrupts the structure of the dividing cell, change the concentration of the various cell constituents and, eventually, the pressure of the converging organelles on

bridge membrane 22 results in the breakage of cell membrane 11 at the vicinity

of the bridge 22, as shown schematically in Fig. 3C. The ability to break

membrane 11 at bridge 22 and to otherwise disrupt the cell structure and

organization can be enhanced by applying a pulsating AC electric field, rather

than a steady AC field. When a pulsating field is applied, the forces acting on

organelles 24 and 26 have a "hammering" effect, whereby pulsed forces beat on

the intracellular organelles towards the neck 22 from both sub-cells 14 and 16,

thereby increasing the probability of breaking cell membrane 11 in the vicinity of

neck 22.

A very important element, which is very susceptible to the special

fields that develop within the dividing cells is the microtubule spindle that plays a

major role in the division process. In Fig. 4, a dividing cell 10 is illustrated, at an

earlier stage as compared to Figs. 3 A and 3B, under the influence of external TC

fields (e.g., alternating fields in the frequency range of about lOOKHz to about

300KHz), generally indicated as lines 100, with a corresponding spindle

mechanism generally indicated at 120. The lines 120 are microtubules that are

known to have a very strong dipole moment. This strong polarization makes the

tubules, as well as other polar macromolecules and especially those that have a specific orientation within the cells or its surrounding, susceptible to electric

fields. Their positive charges are located at the two centrioles while two sets of

negative poles are at the center of the dividing cell and the other pair is at the

points of attachment of the microtubules to the cell membrane, generally

indicated at 130. This structure forms sets of double dipoles and therefore they

are susceptible to fields of different directions. It will be understood that the

effect of the TC fields on the dipoles does not depend on the formation of the

bridge (neck) and thus, the dipoles are influenced by the TC fields prior to the

formation of the bridge (neck).

Since the present apparatus (as will be described in greater detail

below) utilizes insulated electrodes, the above-mentioned negative effects

obtained when conductive electrodes are used, i.e., ion concentration changes in

the cells and the formation of harmful agents by electrolysis, do not occur when

the present apparatus is used. This is because, in general, no actual transfer of

charges takes place between the electrodes and the medium and there is no charge

flow in the medium where the currents are capacitive, i.e., are expressed only as

rotation of charges, etc. Turning now to Fig. 5, the TC fields described above that have

been found to advantageously destroy tumor cells are generated by an electronic

apparatus 200. Fig. 5 is a simple schematic diagram of the electronic apparatus

200 illustrating the major components thereof. The electronic apparatus 200

generates the desired electric signals (TC signals) in the shape of waveforms or

trains of pulses. The apparatus 200 includes a generator 210 and a pair of

conductive leads 220 that are attached at one end thereof to the generator 210.

The opposite ends of the leads 220 are connected to insulated conductors 230 that

are activated by the electric signals (e.g., waveforms). The insulated conductors

230 are also referred to hereinafter as isolects 230. Optionally and according to

another exemplary embodiment, the apparatus 200 includes a temperature sensor

240 and a control box 250 which are both added to control the amplitude of the

electric field generated so as not to generate excessive heating in the area that is

treated.

The generator 210 generates an alternating voltage waveform at

frequencies in the range from about 50KHz to about 500KHz (preferably from

about lOOKHz to about 300KHz) (i.e., the TC fields). The required voltages are

such that the electric field intensity in the tissue to be treated is in the range of

about 0.1 V/cm to about 10 V/cm. To achieve this field, the actual potential difference between the two conductors in the isolects 230 is determined by the

relative impedances of the system components, as described below.

When the control box 250 is included, it controls the output of the

generator 210 so that it will remain constant at the value preset by the user or the

control box 250 sets the output at the maximal value that does not cause

excessive heating, or the control box 250 issues a warning or the like when the

temperature (sensed by temperature sensor 240) exceeds a preset limit.

The leads 220 are standard isolated conductors with a flexible

metal shield, preferably grounded so that it prevents the spread of the electric

field generated by the leads 220. The isolects 230 have specific shapes and

positioning so as to generate an electric field of the desired configuration,

direction and intensity at the target volume and only there so as to focus the

treatment.

The specifications of the apparatus 200 as a whole and its

individual components are largely influenced by the fact that at the frequency of

the present TC fields (50KHz - 500KHz), living systems behave according to

their "Ohmic", rather than their dielectric properties. The only elements in the

apparatus 200 that behave differently are the insulators of the isolects 230 (see Figs. 7-9). The isolects 200 consist of a conductor in contact with a dielectric

that is in contact with the conductive tissue thus forming a capacitor.

The details of the construction of the isolects 230 is based on their

electric behavior that can be understood from their simplified electric circuit

when in contact with tissue as generally illustrated in Fig. 6. In the illustrated

arrangement, the potential drop or the electric field distribution between the

different components is determined by their relative electric impedance, i.e., the

fraction of the field on each component is given by the value of its impedance

divided by the total circuit impedance. For example, the potential drop on

element Δ V_Λ = A/(A+B+C+D+E). Thus, for DC or low frequency AC,

practically all the potential drop is on the capacitor (that acts as an insulator). For

relatively very high frequencies, the capacitor practically is a short and therefore,

practically all the field is distributed in the tissues. At the frequencies of the

present TC fields (e.g., 50KHz to 500KHz), which are intermediate frequencies,

the impedance of the capacitance of the capacitors is dominant and determines

the field distribution. Therefore, in order to increase the effective voltage drop

across the tissues (field intensity), the impedance of the capacitors is to be

decreased (i.e., increase their capacitance). This can be achieved by increasing the effective area of the "plates" of the capacitor, decrease the thickness of the

dielectric or use a dielectric with high dielectric constant.

In order to optimize the field distribution, the isolects 230 are

configured differently depending upon the application in which the isolects 230

are to be used. There are two principle modes for applying the present electric

fields (TC fields). First, the TC fields can be applied by external isolects and

second, the TC fields can be applied by internal isolects.

Electric fields (TC fields) that are applied by external isolects can

be of a local type or widely distributed type. The first type includes, for example,

the treatment of skin tumors and treatment of lesions close to the skin surface.

Fig. 7 illustrates an exemplary embodiment where the isolects 230 are

incorporated in a skin patch 300. The skin patch 300 can be a self-adhesive

flexible patch with one or more pairs of isolects 230. The patch 300 includes

internal insulation 310 (formed of a dielectric material) and the external

insulation 260 and is applied to skin surface 301 that contains a tumor 303 either

on the skin surface 301 or slightly below the skin surface 301. Tissue is

generally indicated at 305. To prevent the potential drop across the internal

insulation 310 to dominate the system, the internal insulation 310 must have a relatively high capacity. This can be achieved by a large surface area; however,

this may not be desired as it will result in the spread of the field over a large area

(e.g., an area larger than required to treat the tumor). Alternatively, the internal

insulation 310 can be made very thin and/or the internal insulation 310 can be of

a high dielectric constant. As the skin resistance between the electrodes (labeled

as A and E in Fig. 6) is normally significantly higher than that of the tissue

(labeled as C in Fig. 6) underneath it (1-10 KΩ vs. 0.1-1KΩ ), most of the

potential drop beyond the isolects occurs there. To accommodate for these

impedances (Z), the characteristics of the internal insulation 310 (labeled as B

and D in Fig. 6) should be such that they have impedance preferably under

100KΩ at the frequencies of the present TC fields (e.g., 50KHz to 500KHz). For

example, if it is desired for the impedance to be about 10K Ohms or less, such

that over 1% of the applied voltage falls on the tissues, for isolects with a surface

area of 10 mm , at frequencies of 200KHz, the capacity should be on the order of

10^"10 F, which means that using standard insulations with a dielectric constant of

2-3, the thickness of the insulating layer 310 should be about 50-100 microns.

An internal field 10 times stronger would be obtained with insulators with a

dielectric constant of about 20-50. Since the thin insulating layer can be very vulnerable, etc., the

insulation can be replaced by very high dielectric constant insulating materials,

such as titanium dioxide (e.g., rutil), the dielectric constant can reach values of

about 200. There a number of different materials that are suitable for use in the

intended application and have high dielectric constants. For example, some

materials include: lithium nibate (LiNbO₃), which is a ferroelectric crystal and

has a number of applications in optical, pyroelectric and piezoelectric devices;

yittrium iron garnet (YIG) is a femmagnetic crystal and magneto-optical devices,

e.g., optical isolator can be realized from this material; barium titanate (BaTiO )

is a ferromagnetic crystal with a large electro-optic effect; potassium tantalate

(KTaO ) which is a dielectric crystal (ferroelectric at low temperature) and has

very low microwave loss and tunability of dielectric constant at low temperature;

and lithium tantalate (LiTaO ) which is a ferroelectric crystal with similar

properties as lithium niobate and has utility in electro-optical, pyroelectric and

piezoelectric devices. It will be understood that the aforementioned exemplary

materials can be used in combination with the present device where it is desired

to use a material having a high dielectric constant.

One must also consider another factor that effects the effective

capacity of the isolects 230, namely the presence of air between the isolects 230 and the skin. Such presence, which is not easy to prevent, introduces a layer of

an insulator with a dielectric constant of 1.0, a factor that significantly lowers the

effective capacity of the isolects 230 and neutralizes the advantages of the

titanium dioxide (routil), etc. To overcome this problem, the isolects 230 can be

shaped so as to conform with the body structure and/or (2) an intervening filler

270 (as illustrated in Fig. 10C), such as a gel, that has high conductance and a

high effective dielectric constant, can be added to the structure. The shaping can

be pre- structured (see Fig. 10A) or the system can be made sufficiently flexible

so that shaping of the isolects 230 is readily achievable. The gel can be contained

in place by having an elevated rim as depicted in Figs. 10C and IOC. The gel

can be made of hydrogels, gelatins, agar, etc., and can have salts dissolved in it to

increase its conductivity. Figs. 10A-10C illustrate various exemplary

configurations for the isolects 230. The exact thickness of the gel is not

important so long as it is of sufficient thickness that the gel layer does not dry out

during the treatment. In one exemplary embodiment, the thickness of the gel is

about 0.5 mm to about 2 mm.

In order to achieve the desirable features of the isolects 230, the

dielectric coating of each should be very thin, for example from between 1-50

microns. Since the coating is so thin, the isolects 230 can easily be damaged mechanically. This problem can be overcome by adding a protective feature to

the isolect' s structure so as to provide desired protection from such damage. For

example, the isolect 230 can be coated, for example, with a relatively loose net

340 that prevents access to the surface but has only a minor effect on the effective

surface area of the isolect 230 (i.e., the capacity of the isolects 230 (cross section

presented in Fig. 12B). The loose net 340 does not effect the capacity and

ensures good contact with the skin, etc. The loose net 340 can be formed of a

number of different materials; however, in one exemplary embodiment, the net

340 is formed of nylon, polyester, cotton, etc. Alternatively, a very thin

conductive coating 350 can be applied to the dielectric portion (insulating layer)

of the isolect 230. One exemplary conductive coating is formed of a metal and

more particularly of gold. The thickness of the coating 350 depends upon the

particular application and also on the type of material used to form the coating

350; however, when gold is used, the coating has a thickness from about 0.1

micron to about 0.1 mm. Furthermore, the rim illustrated in Fig. 10 can also

provide some mechanical protection.

However, the capacity is not the only factor to be considered. The

following two factors also influence how the isolects 230 are constructed. The

dielectric strength of the internal insulating layer 310 and the dielectric losses that occur when it is subjected to the TC field, i.e., the amount of heat generated. The

dielectric strength of the internal insulation 310 determines at what field intensity

the insulation will be "shorted" and cease to act as an intact insulation.

Typically, insulators, such as plastics, have dielectric strength values of about

100V per micron or more. As a high dielectric constant reduces the field within

the internal insulator 310, a combination of a high dielectric constant and a high

dielectric strength gives a significant advantage. This can be achieved by using a

single material that has the desired properties or it can be achieved by a double

layer with the correct parameters and thickness. In addition, to further decreasing

the possibility that the insulating layer 310 will fail, all sharp edges of the

insulating layer 310 should be eliminated as by rounding the corners, etc., as

illustrated in Fig. 10D using conventional techniques.

Figs. 8 and 9 illustrate a second type of treatment using the

isolects 230, namely electric field generation by internal isolects 230. A body to

which the isolects 230 are implanted is generally indicated at 311 and includes a

skin surface 313 and a tumor 315. In this embodiment, the isolects 230 can have

the shape of plates, wires or other shapes that can be inserted subcutaneously or a

deeper location within the body 311 so as to generate an appropriate field at the

target area (tumor 315). It will also be appreciated that the mode of isolects application is

not restricted to the above descriptions. In the case of tumors in internal organs,

for example, liver, lung, etc., the distance between each member of the pair of

isolects 230 can be large. The pairs can even by positioned opposite sides of a

torso 410, as illustrated in Fig. 11. The arrangement of the isolects 230 in Fig. 11

is particularly useful for treating a tumor 415 associated with lung cancer or

gastro-intestinal tumors. In this embodiment, the electric fields (TC fields)

spread in a wide fraction of the body.

In order to avoid overheating of the treated tissues, a selection of

materials and field parameters is needed. The isolects insulating material should

have minimal dielectric losses at the frequency ranges to be used during the

treatment process. This factor can be taken into consideration when choosing the

particular frequencies for the treatment. The direct heating of the tissues will

most likely be dominated by the heating due to current flow (given by the I*R

product). In addition, the isolect (insulated electrode) 230 and its surroundings

should be made of materials that facilitate heat losses and its general structure

should also facilitate head losses, i.e., minimal structures that block heat

dissipation to the surroundings (air) as well as high heat conductivity. The effectiveness of the treatment can be enhanced by an

arrangement of isolects 230 that focuses the field at the desired target while

leaving other sensitive areas in low field density (i.e., protected areas). The

proper placement of the isolects 230 over the body can be maintained using any

number of different techniques, including using a suitable piece of clothing that

keeps the isolects at the appropriate positions. Fig. 13 illustrates such an

arrangement in which an area labeled as "P" represents a protected area. The

lines of field force do not penetrate this protected area and the field there is much

smaller than near the isolects 230 where target areas can be located and treated

well. In contrast, the field intensity near the four poles is very high.

The following Example serves to illustrate an exemplary

application of the present apparatus and application of TC fields; however, this

Example is not limiting and does not limit the scope of the present invention in

any way.

Example

To demonstrate the effectiveness of electric fields having the

above described properties (e.g., frequencies between 50KHz and 500KHz) in

destroying tumor cells, the electric fields were applied to treat mice with malignant melanoma tumors. Two pairs of isolects 230 were positioned over a

corresponding pair of malignant melanomas. Only one pair was connected to the

generator 210 and 200KHz alternating electric fields (TC fields) were applied to

the tumor for a period of 6 days. One melanoma tumor was not treated so as to

permit a comparison between the treated tumor and the non-treated tumor. After

treatment for 6 days, the pigmented melanoma tumor remained clearly visible in

the non-treated side of the mouse, while, in contrast, no tumor is seen on the

treated side of the mouse. The only areas that were visible discemable on the

skin were the marks that represented the points of insertion of the isolects 230.

The fact that the tumor was eliminated at the treated side was further

demonstrated by cutting and inversing the skin so that its inside face was

exposed. Such a procedure indicated that the tumor has been substantially, if not

completely, eliminated on the treated side of the mouse. The success of the

treatment was also further verified by pathhistological examination.

The present inventor has thus uncovered that electric fields having

particular properties can be used to destroy dividing cells or tumors when the

electric fields are applied to using an electronic device. More specifically, these

electric fields fall into a special intermediate category, namely bio-effective fields

that have no meaningful stimulatory and no thermal effects, and therefore overcome the disadvantages that were associated with the application of

conventional electric fields to a body. It will also be appreciated that the present

apparatus can further include a device for rotating the TC field relative to the

living tissue. For example and according to one embodiment, the alternating

electric potential applies to the tissue being treated is rotated relative to the tissue

using conventional devices, such as a mechanical device that upon activation,

rotates various components of the present system.

Moreover and according to yet another embodiment, the TC fields

are applied to different pairs of the insulated electrodes 230 in a consecutive

manner. In other words, the generator 210 and the control system thereof can be

arranged so that signals are sent at periodic intervals to select pairs of insulated

electrodes 230, thereby causing the generation of the TC fields of different

directions by these insulated electrodes 230. Because the signals are sent at

select times from the generator to the insulated electrodes 230, the TC fields of

changing directions are generated consecutively by different insulated electrodes

230. This arrangement has a number of advantages and is provided in view of

the fact that the TC fields have maximal effect when they are parallel to the axis

of cell division. Since the orientation of cell division is in most cases random,

only a fraction of the dividing cells are affected by any given field. Thus, using fields of two or more orientations increases the effectiveness since it increases the

chances that more dividing cells are affected by a given TC field.

Turning now to Fig. 14 in which an article of clothing 500

according to one exemplary embodiment is illustrated. More specifically, the

article of clothing 500 is in the form of a hat or cap or other type of clothing

designed for placement on a head of a person. For purposes of illustration, a head

502 is shown with the hat 500 being placed thereon and against a skin surface

504 of the head 502. An intra-cranial tumor or the like 510 is shown as being

formed within the head 502 underneath the skin surface 504 thereof. The hat 500

is therefore intended for placement on the head 502 of a person who has a tumor

510 or the like.

Unlike the various embodiments illustrated in Figs. 1-13 where the

insulated electrodes 230 are arranged in a more or less planar arrangement since

they are placed either on a skin surface or embedded within the body underneath

it, the insulated electrodes 230 in this embodiment are specifically contoured and

arranged for a specific application. The treatment of intra-cranial tumors or other

lesions or the like typically requires a treatment that is of a relatively long

duration, e.g., days to weeks, and therefore, it is desirable to provide as much comfort as possible to the patient. The hat 500 is specifically designed to provide

comfort during the lengthy treatment process while not jeopardizing the

effectiveness of the treatment.

According to one exemplary embodiment, the hat 500 includes a

predetermined number of insulated electrodes 230 that are preferably positioned

so as to produce the optimal TC fields at the location of the tumor 510. The lines

of force of the TC field are generally indicated at 520. As can be seen in Fig. 14,

the tumor 510 is positioned within these lines of force 520. As will be described

in greater detail hereinafter, the insulated electrodes 230 are positioned within the

hat 500 such that a portion or surface thereof is free to contact the skin surface

504 of the head 502. In other words, when the patient wears the hat 500, the

insulated electrodes 230 are placed in contact with the skin surface 504 of the

head 502 in positions that are selected so that the TC fields generated thereby are

focused at the tumor 510 while leaving surrounding areas in low density.

Typically, hair on the head 502 is shaved in selected areas to permit better contact

between the insulated electrodes 230 and the skin surface 504; however, this is

not critical. The hat 500 preferably includes a mechanism 530 that applies or

force to the insulated electrodes 230 so that they are pressed against the skin

surface 502. For example, the mechanism 530 can be of a biasing type that

applies a biasing force to the insulated electrodes 230 to cause the insulated

electrodes 230 to be directed outwardly away from the hat 500. Thus, when the

patient places the hat 500 on his/her head 502, the insulated electrodes 230 are

pressed against the skin surface 504 by the mechanism 530. The mechanism 530

can slightly recoil to provide a comfortable fit between the insulated electrodes

230 and the head 502. In one exemplary embodiment, the mechanism 530 is a

spring based device that is disposed within the hat 500 and has one section that is

coupled to and applies a force against the insulated electrodes 230.

As with the prior embodiments, the insulated electrodes 230 are

coupled to the generator 210 by means of conductors 220. The generator 210 can

be either disposed within the hat 500 itself so as to provide a compact, self-

sufficient, independent system or the generator 210 can be disposed external to

the hat 500 with the conductors 220 exiting the hat 500 through openings or the

like and then running to the generator 210. When the generator 210 is disposed

external to the hat 500, it will be appreciated that the generator 210 can be

located in any number of different locations, some of which are in close proximity to the hat 500 itself, while others can be further away from the hat 500.

For example, the generator 210 can be disposed within a carrying bag or the like

(e.g., a bag that extends around the patient's waist) which is worn by the patient

or it can be strapped to an extremity or around the torso of the patient. The

generator 210 can also be disposed in a protective case that is secured to or

carried by another article of clothing that is worn by the patient. For example,

the protective case can be inserted into a pocket of a sweater, etc. Fig. 14

illustrates an embodiment where the generator 210 is incorporated directly into

the hat 500.

Turning now to Figs. 15 and 16, in one exemplary embodiment, a

number of insulated electrodes 230 along with the mechanism 530 are preferably

formed as an independent unit, generally indicated at 540, that can be inserted

into the hat 500 and electrically connected to the generator (not shown) via the

conductors (not shown). By providing these members in the form of an

independent unit, the patient can easily insert and/or remove the units 540 from

the hat 500 when they may need cleaning, servicing and/or replacement.

In this embodiment, the hat 500 is constructed to include select

areas 550 that are formed in the hat 500 to receive and hold the units 540. For example and as illustrated in Fig. 15, each area 550 is in the form of an opening

(pore) that is formed within the hat 500. The unit 540 has a body 542 and

includes the mechanism 530 and one or more insulated electrodes 230. The

mechanism 530 is arranged within the unit 540 so that a portion thereof (e.g., one

end thereof) is in contact with a face of each insulated electrode 230 such that the

mechanism 530 applies a biasing force against the face of the insulated electrode

230. Once the unit 540 is received within the opening 550, it can be securely

retained therein using any number of conventional techniques, including the use

of an adhesive material or by using mechanical means. For example, the hat 500

can include pivotable clip members that pivot between an open position in which

the opening 550 is free and a closed position in which the pivotable clip members

engage portions (e.g., peripheral edges) of the insulated electrodes to retain and

hold the insulated electrodes 230 in place. To remove the insulated electrodes

230, the pivotable clip members are moved to the open position. In the

embodiment illustrated in Fig. 16, the insulated electrodes 230 are retained within

the openings 550 by an adhesive element 560 which in one embodiment is a two

sided self-adhesive rim member that extends around the periphery of the

insulated electrode 230. In other words, a protective cover of one side of the

adhesive rim 560 is removed and it is applied around the periphery of the exposed face of the insulated electrode 230, thereby securely attaching the

adhesive rim 560 to the hat 500 and then the other side of the adhesive rim 560 is

removed for application to the skin surface 504 in desired locations for

positioning and securing the insulated electrode 230 to the head 502 with the

tumor being positioned relative thereto for optimization of the TC fields. Since

one side of the adhesive rim 560 is in contact with and secured to the skin surface

540, this is why it is desirable for the head 502 to be shaved so that the adhesive

rim 560 can be placed flushly against the skin surface 540.

The adhesive rim 560 is designed to securely attach the unit 540

within

the opening 550 in a manner that permits the unit 540 to be easily removed from

the hat 500 when necessary and then replaced with another unit 540 or with the

same unit 540. As previously mentioned, the unit 540 includes the biasing

mechanism 530 for pressing the insulated electrode 230 against the skin surface

504 when the hat 500 is worn. The unit 540 can be constructed so that side

opposite the insulated electrode 230 is a support surface formed of a rigid

material, such as plastic, so that the biasing mechanism 530 (e.g., a spring) can be

compressed therewith under the application of force and when the spring 530 is in a relaxed state, the spring 530 remains in contact with the support surface and

the applies a biasing force at its other end against the insulated electrode 230.

The biasing mechanism 530 (e.g., spring) preferably has a contour corresponding

to the skin surface 504 so that the insulated electrode 230 has a force applied

thereto to permit the insulated electrode 230 to have a contour complementary to

the skin surface 504, thereby permitting the two to seat flushly against one

another. While the mechanism 530 can be a spring, there are a number of other

embodiments that can be used instead of a spring. For example, the mechanism

530 can be in the form of an elastic material, such as a foam rubber, a foam

plastic, or a layer containing air bubbles, etc.

The unit 540 has an electric connector 570 that can be hooked up

to a corresponding electric connector, such as a conductor 220, that is disposed

within the hat 500. The conductor 220 connects at one end to the unit 540 and at

the other end is connected to the generator 210. The generator 210 can be

incorporated directly into the hat 500 or the generator 210 can be positioned

separately (remotely) on the patient or on a bedside support, etc.

As previously discussed, a coupling agent, such as a conductive

gel, is preferably used to ensure that an effective conductive environment is provided between the insulated electrode 230 and the skin surface 504. Suitable

gel materials have been disclosed hereinbefore in the discussion of earlier

embodiments. The coupling agent is disposed on the insulated electrode 230 and

preferably, a uniform layer of the agent is provided along the surface of the

electrode 230. One of the reasons that the units 540 need replacement at periodic

times is that the coupling agent needs to be replaced and/or replenished. In other

words, after a predetermined time period or after a number of uses, the patient

removes the units 540 so that the coupling agent can be applied again to the

electrode 230.

Figs. 17 and 18 illustrate another article of clothing which has the

insulated electrodes 230 incorporated as part thereof. More specifically, a bra or

the like 700 is illustrated and includes a body that is formed of a traditional bra

material, generally indicated at 705, to provide shape, support and comfort to the

wearer. The bra 700 also includes a fabric support layer 710 on one side thereof.

The support layer 710 is preferably formed of a suitable fabric material that is

constructed to provide necessary and desired support to the bra 700.

Similar to the other embodiments, the bra 700 includes one or

more insulated electrodes 230 disposed within the bra material 705. The one or more insulated electrodes are disposed along an inner surface of the bra 700

opposite the support 710 and are intended to be placed proximate to a tumor or

the like that is located within one breast or in the immediately surrounding area.

As with the previous embodiment, the insulated electrodes 230 in this

embodiment are specifically constructed and configured for application to a

breast or the immediate area. Thus, the insulated electrodes 230 used in this

application do not have a planar surface construction but rather have an arcuate

shape that is complementary to the general curvature found in a typical breast.

A lining 720 is disposed across the insulated electrodes 230 so as

to assist in retaining the insulated electrodes in their desired locations along the

inner surface for placement against the breast itself. The lining 720 can be

formed of any number of thin materials that are comfortable to wear against one's

skin and in one exemplary embodiment, the lining 720 is formed of a fabric

material.

The bra 700 also preferably includes a biasing mechanism 800 as

in some of the earlier embodiments. The biasing mechanism 800 is disposed

within the bra material 705 and extends from the support 710 to the insulated

electrode 230 and applies a biasing force to the insulated electrode 230 so that the electrode 230 is pressed against the breast. This ensures that the insulated

electrode 230 remains in contact with the skin surface as opposed to lifting away

from the skin surface, thereby creating a gap that results in a less effective

treatment since the gap diminishes the efficiency of the TC fields. The biasing

mechanism 800 can be in the form of a spring arrangement or it can be an elastic

material that applies the desired biasing force to the insulated electrodes 230 so

as to press the insulated electrodes 230 into the breast. In the relaxed position,

the biasing mechanism 800 applies a force against the insulated electrodes 230

and when the patient places the bra 700 on their body, the insulated electrodes

230 are placed against the breast which itself applies a force that counters the

biasing force, thereby resulting in the insulated electrodes 230 being pressed

against the patient's breast. In the exemplary embodiment that is illustrated, the

biasing mechanism 800 is in the form of springs that are disposed within the bra

material 705.

A conductive gel 810 can be provided on the insulated electrode

230 between the electrode and the lining 720. The conductive gel layer 810 is

formed of materials that have been previously described herein for performing

the functions described above. An electric connector 820 is provided as part of the insulated

electrode 230 and electrically connects to the conductor 220 at one end thereof,

with the other end of the conductor 220 being electrically connected to the

generator 210. In this embodiment, the conductor 220 runs within the bra

material 705 to a location where an opening is formed in the bra 700. The

conductor 220 extends through this opening and is routed to the generator 210,

which in this embodiment is disposed in a location remote from the bra 700. It

will also be appreciated that the generator 210 can be disposed within the bra 700

itself in another embodiment. For example, the bra 700 can have a compartment

formed therein which is configured to receive and hold the generator 210 in place

as the patient wears the bra 700. In this arrangement, the compartment can be

covered with a releasable strap that can open and close to permit the generator

210 to be inserted therein or removed therefrom. The strap can be formed of the

same material that is used to construct the bra 700 or it can be formed of some

other type of material. The strap can be releasably attached to the surrounding

bra body by fastening means, such as a hook and loop material, thereby

permitting the patient to easily open the compartment by separating the hook and

loop elements to gain access to the compartment for either inserting or removing

the generator 210. The generator 210 also has a connector 211 for electrical

connection to the conductor 220 and this permits the generator 210 to be

electrically connected to the insulated electrodes 230.

As with the other embodiments, the insulated electrodes 230 are

arranged in the bra 700 to focus the electric field (TC fields) on the desired target

(e.g., a tumor). It will be appreciated that the location of the insulated electrodes

230 within the bra 700 will vary depending upon the location of the tumor. In

other words, after the tumor has been located, the physician will then devise an

arrangement of insulated electrodes 230 and the bra 700 is constructed in view of

this arrangement so as to optimize the effects of the TC fields on the target area

(tumor). The number and position of the insulated electrodes 230 will therefore

depend upon the precise location of the tumor or other target area that is being

treated. Because the location of the insulated electrodes 230 on the bra 700 can

vary depending upon the precise application, the exact size and shape of the

insulated electrodes 230 can likewise vary. For example, if the insulated

electrodes 230 are placed on the bottom section of the bra 700 as opposed to a

more central location, the insulated electrodes 230 will have different shapes

since the shape of the breast (as well as the bra) differs in these areas. Fig. 19 illustrates yet another embodiment in which the insulated

electrodes 230 are in the form of internal electrodes that are incorporated into in

the form of a probe or catheter 600 that is configured to enter the body through a

natural pathway, such as the urethra, vagina, etc. In this embodiment, the

insulated electrodes 230 are disposed on an outer surface of the probe 600 and

along a length thereof. The conductors 220 are electrically connected to the

electrodes 230 and run within the body of the probe 600 to the generator 210

which can be disposed within the probe body or the generator 210 can be

disposed independent of the probe 600 in a remote location, such as on the patient

or at some other location close to the patient.

Alternatively, the probe 600 can be configured to penetrate the

skin surface or other tissue to reach an internal target that lies within the body.

For example, the probe 600 can penetrate the skin surface and then be positioned

adjacent to or proximate to a tumor that is located within the body.

In these embodiments, the probe 600 is inserted through the

natural pathway and then is positioned in a desired location so that the insulated

electrodes 230 are disposed near the target area (i.e., the tumor). The generator

210 is then activated to cause the insulated electrodes 230 to generate the TC fields which are applied to the tumor for a predetermined length of time. It will

be appreciated that the illustrated probe 600 is merely exemplary in nature and

that the probe 600 can have other shapes and configurations so long as they can

perform the intended function. Preferably, the conductors (e.g., wires) leading

from the insulated electrodes 230 to the generator 210 are twisted or shielded so

as not to generate a field along the shaft.

It will further be appreciated that the probes can contain only one

insulated electrode while the other can be positioned on the body surface. This

external electrode should be larger or consist of numerous electrodes so as to

result in low lines of force -current density so as not to affect the untreated areas.

In fact, the placing of electrodes should be designed to minimize the field at

potentially sensitive areas.

Fig. 20 illustrates yet another embodiment in which a high

standing collar member 900 (or necklace type structure) can be used to treat

thyroid, parathyroid, laryngeal lesions, etc. Fig. 20 illustrates the collar member

900 in an unwrapped, substantially flat condition. In this embodiment, the

insulated electrodes 230 are incorporated into a body 910 of the collar member

900 and are configured for placement against a neck area of the wearer. The insulated electrodes 230 are coupled to the generator 210 according to any of the

manner described hereinbefore and it will be appreciated that the generator 210

can be disposed within the body 910 or it can be disposed in a location external to

the body 910. The collar body 910 can be formed of any number of materials

that are traditionally used to form collars 900 that are disposed around a person's

neck. As such, the collar 900 preferably includes a means 920 for adjusting the

collar 900 relative to the neck. For example, complementary fasteners (hook and

loop fasteners, buttons, etc.) can be disposed on ends of the collar 900 to permit

adjustment of the collar diameter.

Thus, the construction of the present devices are particularly well

suited for applications where the devices are incorporated into articles of clothing

to permit the patient to easily wear a traditional article of clothing while at the

same time the patient undergoes treatment. In other words, an extra level of

comfort can be provided to the patient and the effectiveness of the treatment can

be increased by incorporating some or all of the device components into the

article of clothing. The precise article of clothing that the components are

incorporated into will obviously vary depending upon the target area of the living

tissue where tumor, lesion or the like exists. For example, if the target area is in

the testicle area of a male patient, then an article of clothing in the form of a sock-like structure or wrap can be provided and is configured to be worn around

the testicle area of the patient in such a manner that the insulated electrodes

thereof are positioned relative to the tumor such that the TC fields are directed at

the target tissue. The precise nature or form of the article of clothing can vary

greatly since the device components can be incorporated into most types of

articles of clothing and therefore, can be used to treat any number of different

areas of the patient's body where a condition may be present.

Now turning to Figs. 21-22 in which another aspect of the present

device is shown. In Fig. 21, a body 1000, such as any number of parts of a

human or animal body, is illustrated. As in the previous embodiments, two or

more insulated electrodes 230 are disposed in proximity to the body 1000 for

treatment of a tumor or the like (not shown) using TC fields, as has been

previously described in great detail in the above discussion of other

embodiments. The insulated electrode 230 has a conductive component and has

external insulation 260 that surrounds the conductive component thereof. Each

insulated electrode 230 is preferably connected to a generator (not shown) by the

lead 220. Between each insulated electrode 220 and the body 1000, a conductive

filler material (e.g., conductive gel member 270) is disposed. The insulated

electrodes 230 are spaced apart from one another and when the generator is actuated, the insulated electrodes 230 generate the TC fields that have been

previously described in great detail. The lines of the electric field (TC field) are

generally illustrated at 1010. As shown, the electric field lines 1010 extend

between the insulated electrodes 230 and through the conductive gel member

270.

Over time or as a result of some type of event, the external

insulation 260 of the insulated electrode 230 can begin to breakdown at any given

location thereof. For purpose of illustration only, Fig. 22 illustrates that the

external insulation 260 of one of the insulated electrodes 230 has experienced a

breakdown 1020 at a face thereof which is adjacent the conductive gel member

270. It will be appreciated that the breakdown 1020 of the external insulation

260 results in the formation of a strong current flow-current density at this point

(i.e., at the breakdown 1020). The increased current density is depicted by the

increased number of electric field lines 1010 and the relative positioning and

distance between adjacent electric field lines 1010. One of the side effects of the

occurrence of breakdown 1020 is that current exists at this point which will

generate heat and may burn the tissues/skin which have a resistance. In Fig. 22,

an overheated area 1030 is illustrated and is a region or area of the tissues/skin

where an increased current density exits due to the breakdown 1020 in the external insulation 260. A patient can experience discomfort and pain in this area

1030 due to the strong current that exists in the area and the increased heat and

possible burning sensation that exist in area 1030.

Fig. 23 illustrates yet another embodiment in which a further

application of the insulated electrodes 230 is shown. In this embodiment, the

conductive gel member 270 that is disposed between the insulated electrode 230

and the body 1000 includes a conductor 1100 that is floating in that the gel

material forming the member 270 completely surrounds the conductor 1100. In

one exemplary embodiment, the conductor 1100 is a thin metal sheet plate that is

disposed within the conductor 1100. As will be appreciated, if a conductor, such

as the plate 1100, is placed in a homogeneous electric field, normal to the lines of

the electric field, the conductor 1100 practically has no effect on the field (except

that the two opposing faces of the conductor 1100 are equipotential and the

corresponding equipotentials are slightly shifted). Conversely, if the conductor

1100 is disposed parallel to the electric field, there is a significant distortion of

the electric field. The area in the immediate proximity of the conductor 1100 is

not equipotential, in contrast to the situation where there is no conductor 1100

present. When the conductor 1100 is disposed within the gel member 270, the

conductor 1100 will typically not effect the electric field (TC field) for the reasons discussed above, namely that the conductor 1100 is normal to the lines of

the electric field.

If there is a breakdown of the external insulation 260 of the

insulated electrode 230, there is a strong current flow-current density at the point

of breakdown as previously discussed; however, the presence of the conductor

1100 causes the current to spread throughout the conductor 1100 and then exit

from the whole surface of the conductor 1100 so that the current reaches the body

1000 with a current density that is neither high nor low. Thus, the current that

reaches the skin will not cause discomfort to the patient even when there has been

a breakdown in the insulation 260 of the insulated electrode 230. It is important

that the conductor 1100 is not grounded as this would cause it to abolish the

electric field beyond it. Thus, the conductor 1100 is "floating" within the gel

member 270.

If the conductor 1100 is introduced into the body tissues 1000 and

is not disposed parallel to the electric field, the conductor 1100 will cause

distortion of the electric field. The distortion can cause spreading of the lines of

force (low field density-intensity) or concentration of the lines of field (higher

density) of the electric field, according to the particular geometries of the insert and its surroundings, and thus, the conductor 1100 can exhibit, for example, a

screening effect. Thus, for example, if the conductor 1100 completely encircles

an organ 1101, the electric field in the organ itself will be zero since this type of

arrangement is a Faraday cage. However, because it is impractical for a

conductor to be disposed completely around an organ, a conductive net or similar

structure can be used to cover, completely or partially, the organ, thereby

resulting in the electric field in the organ itself being zero or about zero. For

example, a net can be made of a number of conductive wires that are arranged

relative to one another to form the net or a set of wires can be arranged to

substantially encircle or otherwise cover the organ 1101. Conversely, an organ

1103 to be treated (the target organ) is not covered with a member having a

Faraday cage effect but rather is disposed in the electric field 1010 (TC fields).

Fig. 24 illustrates an embodiment where the conductor 1100 is

disposed within the body (i.e., under the skin) and it is located near a target (e.g.,

a target organ). By placing the conductor 1100 near the target, high field density

(of the TC fields) is realized at the target. At the same time, another nearby

organ can be protected by disposing the above described protective conductive

net or the like around this nearby organ so as to protect this organ from the fields.

By positioning the conductor 1100 in close proximity to the target, a high field density condition can be provided near or at the target. In other words, the

conductor 1100 permits the TC fields to be focused at a particular area (i.e., a

target).

It will also be appreciated that in the embodiment of Fig. 24, the

gel members 260 can each include a conductor as described with reference to Fig.

23. In such an arrangement, the conductor in the gel member 260 protects the

skin surface (tissues) from any side effects that may be realized if a breakdown in

the insulation of the insulated electrode 230 occurs. At the same time, the

conductor 1100 creates a high field density near the target.

There are a number of different ways to tailor the field density of

the electric field by constructing the electrodes differently and/or by strategically

placing the electrodes relative to one another. For example, in Fig. 25, a first

insulated electrode 1200 and a second insulated electrode 1210 are provided and

are disposed about a body 1300. Each insulated electrode includes a conductor

that is preferably surrounded by an insulating material, thus the term "insulated

electrode". Between each of the first and second electrodes 1200, 1210 and the

body 1300, the conductive gel member 270 is provided. Electric field lines are

generally indicated at 1220 for this type of arrangement. In this embodiment, the first insulated electrode 1200 has dimensions that are significantly greater than

the dimensions of the second insulated electrode 1210 (the conductive gel

member for the second insulated electrode 1210 will likewise be smaller).

By varying the dimensions of the insulated electrodes, the pattern

of the electric field lines 1220 is varied. More specifically, the electric field

tapers inwardly toward the second insulated electrode 1210 due to the smaller

dimensions of the second insulated electrode 1210. An area of high field density,

generally indicated at 1230, forms near the interface between the gel member 270

associated with the second insulated electrode 1210 and the skin surface. The

various components of the system are manipulated so that the tumor within the

skin or on the skin is within this high field density so that the area to be treated

(the target) is exposed to electric field lines of a higher field density.

Fig. 26 also illustrates a tapering TC field when a conductor 1400

(e.g., a conductive plate) is disposed in each of the conductive gel members 270.

In this embodiment, the size of the gel members 270 and the size of the

conductors

1400 are the same or about the same despite the differences in the sizes of the

insulated electrodes 1200, 1210. The conductors 1400 again can be characterized as "floating plates" since each conductor 1400 is surrounded by the material that

forms the gel member 270. As shown in Fig. 26, the placement of one conductor

1400 near the insulated electrode 1210 that is smaller than the other insulated

electrode 1200 and is also smaller than the conductor 1400 itself and the other

insulated electrode 1200 is disposed at a distance therefrom, the one conductor

1400 causes a decrease in the field density in the tissues disposed between the

one conductor 1400 and the other insulated electrode 1200. The decrease in the

field density is generally indicated at 1410. At the same time, a very

inhomogeneous tapering field, generally indicated at 1420, changing from very

low density to very high density is formed between the one conductor 1400 and

the insulated electrode 1210. One benefit of this exemplary configuration is that

it permits the size of the insulated electrode to be reduced without causing an

increase in the nearby field density. This can be important since electrodes that

having very high dielectric constant insulation can be very expensive. For

example, one insulated electrode can cost $500.00 or more and further, the price

is sensitive to the particular area of treatment. Thus, a reduction in the size of the

insulated electrodes directly leads to a reduction in cost.

While the invention has been particularly shown and described

with reference to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details can be made without

departing from the spirit and scope of the invention.

Claims

WHAT IS CLAIMED IS:

1. An apparatus for selectively destroying dividing cells in

living tissue, the dividing cells having polarizable or polar intracellular members,

the apparatus comprising:

a first insulated electrode having a first conductor;

a second insulated electrode having a second conductor; and

an electric field source for applying an alternating electric

potential

across the first and second conductors, wherein passage of the electric field

through the dividing cells in late anaphase or telophase transforms the electric

field into a non-homogenous electric field that produces an increased density

electric field in a region of a cleavage furrow of the dividing cells, the non-

homogeneous electric field produced within the dividing cells being of sufficient

intensity to move the polarizable intracellular members toward the cleavage.

2. The apparatus of claim 1, wherein the electric field is of

sufficient frequency so that the non-homogeneous electric field produced in the

dividing cells defines electric field lines which generally converge at a region of

the cleavage furrow, thereby defining the increased density electric field, resulting in destruction of the dividing cells as a result of the polarizable

intracellular members movement toward the furrow.

3. The apparatus of claim 1, further including:

a first conductive lead operatively connecting the first electrode to

the electric field source; and

a second conductive lead operatively connecting the second

electrode to the electric field source.

4. The apparatus of claim 1, wherein the first electrode

includes a first dielectric member that is in contact with the first conductor, the

first dielectric member for placement against the living tissue to form a capacitor,

wherein the second electrode includes a second dielectric member that is in

contact with the second conductor, the second dielectric member for placement

against the living tissue to form a capacitor.

5. The apparatus of claim 4, wherein each of the first and

second dielectric members is formed of a layer of titanium dioxide.

6. The apparatus of claim 4, wherein each of the first and

second dielectric members comprises a dielectric coating having a thickness

between about 5 microns to about 50 microns.

7. The apparatus of claim 6, further including: a loose net disposed around the dielectric coating for restricting

access to a surface of the dielectric coating while only having a minimal effect on

a surface area of the dielectric coating.

8. The apparatus of claim 6, further including:

a thin conducting coating disposed on the dielectric coating for

contacting the tissue.

9. The apparatus of claim 8, wherein the conducting coating

is formed of gold.

10. The apparatus of claim 1, wherein the alternating electric

potential has a frequency of between about lOOKHz to about 300KHz.

11. The apparatus of claim 1, wherein the electric field source

comprises a generator that generates an alternating voltage waveform at

frequencies between about 50KHz to about 500KHz.

12. The apparatus of claim 11, wherein the voltage waveform

is selected so that an electric field intensity in tissue to be treated is between

about 0.1 V/cm to about 10.0 V/cm.

13. The apparatus of claim 4, wherein at least one of the first

and second electrodes includes an intervening filler disposed on the respective dielectric member thereof, the intervening filler being formed of a material that

has high conductance and a high dielectric constant.

14. The apparatus of claim 13, wherein the intervening filler

comprises a gel formed of at least one material selected from the group consisting

of gelatins and agar.

15. The apparatus of claim 13, wherein the intervening filler is

contained within the dielectric member by a rim formed as part of the dielectric

member.

16. A skin patch for selectively destroying dividing cells that

are in a localized area of living tissue, the dividing cells having polarizable or

polar intracellular members, the skin patch including:

a skin patch body for placement on the living tissue over the

localized area of dividing cells, the skin patch body comprising:

a first insulated electrode having a first conductor;

a second insulated electrode having a second conductor;

and

an electric field source for applying an alternating electric

potential across the first and second conductors, wherein passage of the electric field

through the dividing cells in late anaphase or telophase transforms the electric

field into a non-homogenous electric field that produces an increased density

electric field in a region of a cleavage furrow of the dividing cells, the non-

homogeneous electric field produced within the dividing cells being of sufficient

intensity to move the polarizable intracellular members toward the cleavage

furrow.

17. The skin patch of claim 16, wherein the electric field is of

sufficient frequency so that the non-homogeneous electric field produced in the

dividing cells defines electric field lines which generally converge at a region of

the cleavage furrow, thereby defining the increased density electric field ,

resulting in destruction of the dividing cells as a result of the polarizable

intracellular members movement toward the furrow.

18. The skin patch of claim 16, wherein the alternating electric

potential has a frequency of between about lOOKHz to about 300KHz.

19. An article of clothing having a feature for selectively

destroying dividing cells in a target area of living tissue, the dividing cells having

polarizable or polar or charged intracellular members, the article of clothing

being constructed to be worn over the target area and comprising: a first insulated electrode having a first conductor;

a second insulated electrode having a second conductor; and

an electric field source connected to the first and second insulated

electrodes for applying an alternating electric potential difference across the first

and second conductors, wherein passage of the electric field through the dividing

cells in late anaphase or telophase transforms the electric field into a non-

homogenous electric field that produces an increased density electric field in a

region of a cleavage furrow of the dividing cells, the non-homogeneous electric

field produced within the dividing cells being of sufficient intensity to move the

polarizable or charged intracellular members toward the cleavage furrow.

20. The article of clothing of claim 19, wherein the article

comprises a hat to be worn over a head for treatment of one of an intra-cranial

tumor and a scalp tumor.

21. The article of clothing of claim 20, wherein the first and

second insulated electrodes have an arcuate shape for placement against the head.

22. The article of clothing of claim 19, wherein the electric

field is of sufficient frequency so that the non-homogeneous electric field

produced in the dividing cells defines electric field lines which generally

converge at a region of the cleavage furrow, thereby defining the increased density electric field , resulting in destruction of the dividing cells as a result of

the polarizable intracellular members movement toward the cleavage furrow.

23. The article of clothing of claim 19, further including:

a first conductive lead operatively connecting the first electrode to

the electric field source; and

a second conductive lead operatively connecting the second

electrode to the electric field source.

24. The article of clothing of claim 19, wherein the first

electrode includes a first dielectric member that is in contact with the first

conductor, the first dielectric member for placement against the living tissue to

form a capacitor and wherein the second electrode includes a second dielectric

member that is in contact with the second conductor, the second dielectric

member for placement against the living tissue to form a capacitor.

25. The article of clothing of claim 19, wherein the alternating

electric potential has a frequency of between about 50KHz to about 500KHz.

26. The article of clothing of claim 19, wherein the alternating

electric potential has a frequency of between about lOOKHz to about 300KHz.

27. The article of clothing of claim 19, wherein the electric

field source comprises a generator that generates an alternating voltage waveform

at frequencies between about 50KHz to about 500KHz.

28. The article of clothing of claim 27, wherein the generator is

disposed within the article of clothing.

29. The article of clothing of claim 19, further including:

a biasing mechanism for biasing each of the first and second

electrodes in a direction toward the living tissue when the article of clothing is

worn to ensure that the first and second electrodes seat against the living tissue.

30. The article of clothing of claim 29, wherein the biasing

mechanism includes a spring that applies a biasing force against one of the first

and second electrodes in the direction toward the living tissue.

31. The article of clothing of claim 29, wherein the biasing

mechanism comprises a body formed of an elastic material that is disposed within

the article of clothing in close proximity to or in contact with one of the insulated

electrodes.

32. The article of clothing of claim 31, wherein the body is

formed of a material that has undergone a foaming process.

33. The article of clothing of claim 19, wherein each insulated

electrode includes a conductor and a dielectric member in contact therewith and

for placement against the living tissue to form a capacitor.

34. The article of clothing of claim 33, wherein the insulated

electrode includes an intervening filler disposed on the respective dielectric

member thereof, the intervening filler being formed of a material that has high

conductance and a high dielectric constant.

35. The article of clothing of claim 34, wherein the intervening

filler comprises a gel formed of at least one material selected from the group

consisting of hydrogels, gelatins and agar.

36. The article of clothing of claim 19, wherein the clothing is

in the form of a bra.

37. A hat for treatment of an intra-cranial tumor or lesion by

selectively destroying dividing cells of the tumor, the dividing cells having

polarizable or polar or charged intracellular members, the hat comprising:

a hat body to be worn over a head and including a predetermined

number of openings formed therein;

at least one insulated electrode unit for placement in one of the

openings of the hat, each unit being a member having an insulated electrode disposed at one face thereof and a biasing mechanism for applying a biasing force

against the insulated electrode in a direction away from the hat body, the

insulated electrode being disposed at one face of the hat body when the unit is

inserted and securely held within the opening; and

an electric field source for applying an alternating electric

potential across at least two insulated electrodes to create a condition in the

dividing cells that results in the destruction thereof.

38. The hat of claim 37, wherein the unit is securely retained

within the opening by an adhesive member that has an adhesive layer formed on

at least one side thereof, the adhesive member being disposed around a peripheral

edge of the insulated electrode and over a peripheral edge of the hat body around

the opening for securely positioning and retaining the unit within the opening

with the insulated electrode being positioned at one face of the hat body.

39. The hat of claim 37, wherein the electric field source

comprises a generator that generates an alternating voltage waveform at

frequencies between about 50KHz to about 500KHz that activate each insulated

electrode.

40. The hat of claim 39, wherein the generator is disposed

within the hat body.

41. The hat of claim 37, wherein the biasing mechanism

includes a spring that applies a biasing force against one of the first and second

electrodes in the direction toward the living tissue.

42. The hat of claim 41 , wherein the biasing mechanism is

contained within a unit that is detachably coupled to the hat to permit removal

and replacement thereof.

43. The hat of claim 37, wherein the biasing mechanism

comprises a body formed of an elastic material that is disposed within the article

of clothing in close proximity to or in contact with one of the insulated electrodes.

44. The hat of claim 37, wherein each insulated electrode

includes a conductor and a dielectric member in contact therewith and for

placement against the head to form a capacitor.

45. The hat of claim 44, wherein the insulated electrode

includes an intervening filler disposed on the respective dielectric member

thereof, the intervening filler being formed of a material that has high

conductance and a high dielectric constant.

46. A probe for treatment of a section of living tissue by

selectively destroying dividing cells of a target section of tissue, the dividing

cells having polarizable or polar intracellular members, the probe comprising: a probe body for insertion into a body;

at least two insulated electrodes disposed on an outer surface of

the probe body; and

an electric field source for applying an alternating electric

potential across the at least two insulated electrodes to create a condition in the

dividing cells that encourages the destruction thereof.

47. The probe of claim 46, wherein the probe body is

configured to be inserted into and pass through a natural pathway of the body to

position the insulated electrodes relative to the target section.

48. The probe of claim 46, wherein the probe body is

configured to penetrate the living tissue and be positioned so that the electrodes

are disposed proximate the target section.

49. The probe of claim 46, wherein the first and second

insulated electrodes have an arcuate shape.

50. The probe of claim 46, wherein the electric field source

comprises a generator that generates an alternating voltage waveform at

frequencies between about 50KHz to about 500KHz that activate each insulated

electrode.

51. An apparatus for selectively destroying dividing cells in a

target area of living tissue, the dividing cells having polarizable or polar or

charged intracellular members, the apparatus comprising:

a first insulated electrode having a first conductor;

a second insulated electrode having a second conductor;

an electric field source connected to the first and second insulated

electrodes for applying an alternating electric potential difference across the first

and second conductors to create a condition in the dividing cells that encourages

the destruction thereof;

an intervening member formed of a filler material disposed

between one of the first and second insulated electrodes and a skin surface, the

filler material having a high conductance; and

a third conductor disposed within the intervening member such

that the filler material of the intervening member completely surrounds the third

conductor.

52. The apparatus of claim 51 , wherein passage of the electric

field through the dividing cells in late anaphase or telophase transforms the

electric field into a non-homogenous electric field that produces an increased

density electric field in a region of a cleavage furrow of the dividing cells, the non-homogeneous electric field produced within the dividing cells being of

sufficient intensity to move the polarizable, polar or charged intracellular

members toward the cleavage.

53. The apparatus of claim 51 , wherein the third conductor

disposed within the intervening member comprises a flat conductor plate.

54. The apparatus of claim 51 , wherein a length of the third

conductor is equal to or about equal to a length of each of the first and second

conductors.

55. The apparatus of claim 51 , further including:

a first conductive lead operatively connecting the first electrode to

the electric field source; and

a second conductive lead operatively connecting the second

electrode to the electric field source.

56. The apparatus of claim 51 , wherein the first electrode

includes a first dielectric member that is in contact with the first conductor, the

first dielectric member for placement against the living tissue to form a capacitor

and wherein the second electrode includes a second dielectric member that is in

contact with the second conductor, the second dielectric member for placement

against the living tissue to form a capacitor.

57. The apparatus of claim 51, wherein the alternating electric

potential has a frequency of between about 50KHz to about 500KHz.

58. The apparatus of claim 51 , wherein the first insulated

electrode is of a first size and the second insulated electrode is of a second size

that is greater than the first size, the intervening member associated with the first

insulated electrode being of a smaller size than the intervening member

associated with the second insulated electrode.

59. The apparatus of claim 58, wherein the electric field near

the first insulated electrode is of a higher field density than the electric field in

other locations between the first and second insulated electrodes.

60. The apparatus of claim 59, wherein the electric field tapers

inwardly to the first insulated electrode.

61. The apparatus of claim 51 , wherein the intervening filler

comprises a gel formed of at least one material selected from the group consisting

of hydrogels, gelatins and agar.

62. An apparatus for selectively destroying dividing cells in a

target area of living tissue, the dividing cells having polarizable or polar or

charged intracellular members, the apparatus comprising:

a first insulated electrode having a first conductor; a second insulated electrode having a second conductor;

an electric field source connected to the first and second insulated

electrodes for applying an alternating electric potential difference across the first

and second conductors to create a condition in the dividing cells that encourages

the destruction thereof;

an intervening member disposed between one of the first and

second insulated electrodes and a skin surface, the intervening member being

formed of a filler material that has a high conductance and a high dielectric

constant; and

wherein the first insulated electrode is of a first size and the

second insulated electrode is of a second size that is greater than the first size, the

intervening member associated with the first insulated electrode being of a

smaller size than the intervening member associated with the second insulated

electrode, resulting in the electric field near the first insulated electrode being of a

higher field density than the electric field in other locations between the first and

second insulated electrodes.

63. The apparatus of claim 62, wherein the electric field tapers

inwardly to the first insulated electrode.

64. The apparatus of claim 62, wherein the first electrode

includes a first dielectric member that is in contact with the first conductor, the

first dielectric member for placement against the living tissue to form a capacitor

and wherein the second electrode includes a second dielectric member that is in

contact with the second conductor, the second dielectric member for placement

against the living tissue to form a capacitor.

65. The apparatus of claim 62, wherein the alternating electric

potential has a frequency of between about 50KHz to about 500KHz.

66. The apparatus of claim 62, wherein the electric field source

comprises a generator that generates an alternating voltage waveform at

frequencies between about 50KHz to about 500KHz.

67. The apparatus of claim 62, wherein the intervening filler

comprises a gel formed of at least one material selected from the group consisting

of hydrogels, gelatins and agar.

68. An apparatus for selectively destroying dividing cells in a

target area of living tissue, the dividing cells having polarizable or polar or

charged intracellular members, the apparatus comprising:

a first insulated electrode having a first conductor;

a second insulated electrode having a second conductor; an electric field source connected to the first and second insulated

electrodes for applying an alternating electric potential difference across the first

and second conductors to create a condition in the dividing cells that encourages

the destruction thereof;

an intervening member disposed each of the first and second

insulated electrodes and a skin surface, each intervening member being formed of

a filler material having a high conductance and a high dielectric constant; and

a third conductor disposed within the living tissue in close

proximity to the target area and between the first and second insulated electrodes,

the third conductor causing increased electric field density in the target area.

69. The apparatus of claim 68, further including:

a conductor protective member that is disposed around an organ to

be shielded and protected from effects of an electric field generated by the

electric field source.

70. The apparatus of claim 69, wherein the conductive

protective member comprises a net formed of conductive elements that is

disposed around at least a portion of the organ to be protected.

71. The apparatus of claim 68, wherein each insulated

electrode includes a conductor and a dielectric member in contact therewith and

for placement against the living tissue to form a capacitor.

72. The apparatus of claim 68, wherein the intervening filler

comprises a gel formed of at least one material selected from the group consisting

of hydrogels, gelatins and agar.

73. The apparatus of claim 72, wherein the gel includes salt

dissolved therein to increase the conductivity of the gel.