Patent Description:
TTFields are typically delivered through two pairs of transducer arrays that generate perpendicular fields within the treated tumor. The transducer arrays that make up each of these pairs are positioned on opposite sides of the body part that is being treated. For example, in using the OPTUNE® system (manufactured by Novocure Limited, having a principle place of business in St. Helier, Jersey), at least one pair of electrodes of the transducer array is located to the left and right (LR) of the tumor, and at least one pair of electrodes is located anterior and posterior (AP) to the tumor.

Each transducer array used for the delivery of TTFields in the OPTUNE® system comprises at least one set of non-conductive ceramic disk electrodes coupled to the patient's skin. For example, the OPTUNE® system may position the transducer arrays on a patient's shaved head (e.g., treatment of Glioblastoma, hereinafter 'GBM') with the non-conductive ceramic disk electrodes coupled to the patient's skin through a layer of conductive medical gel.

To form the ceramic disk electrodes, a conductive layer is formed on a top surface of nonconductive ceramic material. A bottom surface of the nonconductive ceramic material is coupled to the conductive medical gel. The nonconductive ceramic material is a safety feature to ensure that direct-current signals are blocked from unintentionally being transmitted to the patient. By interposing a nonconductive ceramic material between the conductive layer and the conductive medical gel, the prior art system was thought to ensure the patient remains protected. The medical gel may deform to match the body's contours and provide electrical contact between the arrays and the skin; as such, the medical gel interface bridges the skin and reduces interference. The device is intended to be continuously worn by the patient for two to fourdays before removal for hygienic care and re-shaving (if necessary), followed by reapplication with a new set of arrays. As such, the medical gel remains in substantially continuous contact with an area of the patient's skin for a period of <NUM>-<NUM> days at a time. Further, there may only be a brief period of time in which the area of skin is uncovered and exposed to the environment before more medical gel is applied thereto.

Conventionally, the medical gel is applied manually to the electrode elements, which is a labor-intensive, tedious and expensive procedure. Further, the medical gel has a tendency to move laterally on the patient.

As such, new and improved array assemblies, and methods of making the array assemblies that speed up manufacturing and anchor the medical gel to the electrode arrays to reduce lateral movement of the medical gel is desired. It is to such assemblies and methods of producing and using the same, that the present disclosure is directed.

<CIT> discloses an electrode providing electrical contact with a patient's skin, which includes a conductive member adapted for connection to an external electrical apparatus and a multilayer system for providing an electrical interface between the patient's skin and the conductive member, where the multilayer system includes a first layer of an electrically-conductive gel, having a relatively-low peel strength, for removably contacting the patient's skin, and a second layer of an electrically-conductive gel, having a relatively-high peel strength, for contacting the conductive member.

<CIT> discloses a transducer array for use in tumor-treating fields (TTFields) therapy, which has a branching configuration and includes a branching top covering, adhesive-backed layer and a skin-level adhesive layer to which electrode elements are attached.

The present invention relates to a method of producing gel elements according to claim <NUM>.

Before explaining at least one embodiment of the inventive concept(s) in detail by way of exemplary language and results, it is to be understood that the inventive concept(s) is not limited in its application to the details of construction and the arrangement of the components set forth in the following description. The inventive concept(s) is capable of other embodiments or of being practiced or carried out in various ways. As such, the language used herein is intended to be given the broadest possible scope and meaning; and the embodiments are meant to be exemplary - not exhaustive.

Unless otherwise defined herein, scientific and technical terms used in connection with the presently disclosed inventive concept(s) shall have the meanings that are commonly understood by those of ordinary skill in the art.

As utilized in accordance with the present disclosure, the following terms, unless otherwise indicated, shall be understood to have the following meanings:
The use of the term "a" or "an" when used in conjunction with the term "comprising" in the claims and/or the specification may mean "one," but it is also consistent with the meaning of "one or more," "at least one," and "one or more than one. " As such, the terms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. Thus, for example, reference to "a compound" may refer to one or more compounds, two or more compounds, three or more compounds, four or more compounds, or greater numbers of compounds. The term "plurality" refers to "two or more.

The use of the term "at least one" will be understood to include one as well as any quantity more than one, including but not limited to, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, etc. In addition, the use of the term "at least one of X, Y, and Z" will be understood to include X alone, Y alone, and Z alone, as well as any combination of X, Y, and Z. The use of ordinal number terminology (i.e., "first," "second," "third," "fourth," etc.) is solely for the purpose of differentiating between two or more items and is not meant to imply any sequence or order or importance to one item over another or any order of addition, for example.

The use of the term "or" in the claims is used to mean an inclusive "and/or" unless explicitly indicated to refer to alternatives only or unless the alternatives are mutually exclusive. For example, a condition "A or B" is satisfied by any of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).

As used herein, any reference to "one embodiment," "an embodiment," "some embodiments," "one example," "for example," or "an example" means that a particular element, feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. The appearance of the phrase "in some embodiments" or "one example" in various places in the specification is not necessarily all referring to the same embodiment, for example. Further, all references to one or more embodiments or examples are to be construed as non-limiting to the claims.

Throughout this application, the term "about" is used to indicate that a value includes the inherent variation of error for a composition/apparatus/ device, the method being employed to determine the value, or the variation that exists among the study subjects.

As used in this specification and claim(s), the words "comprising" (and any form of comprising, such as "comprise" and "comprises"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include"), or "containing" (and any form of containing, such as "contains" and "contain") are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

As used herein, the term "substantially" means that the subsequently described event or circumstance completely occurs or that the subsequently described event or circumstance occurs to a great extent or degree. For example, when associated with a particular event or circumstance, the term "substantially" means that the subsequently described event or circumsta nce occurs at least <NUM>% of the time, or at least <NUM>% of the time, or at least <NUM>% of the time, or at least <NUM>% of the time. For example, the term "substantially adjacent" may mean that two items are <NUM>% adjacent to one another, or that the two items are within close proximity to one another but not <NUM>% adjacent to one another, or that a portion of one of the two items is not <NUM>% adjacent to the other item but is within close proximity to the other item.

The term "patient" as used herein includes human and veterinary subjects. "Mammal" for purposes of treatment refers to any animal classified as a mammal, including (but not limited to) humans, domestic and farm animals, nonhuman primates, and any other animal that has mammary tissue.

The term "liquid hydrogel" and "flowable hydrogel" as used herein may be understood to refer to an uncured hydrogel formulation that is in an at least partially flowable form. That is, the term "liquid hydrogel" refers to a hydrogel formulation prior to curing and that is curable by ultraviolet (UV) radiation or ionizing high energy radiation.

Referring now to the drawings and in particular to <FIG>, shown therein is an exemplary embodiment of a dividing cell <NUM>, under the influence of external TTFields <NUM>. In some embodiments, external TTFields may include alternating fields <NUM> in the frequency range of about <NUM> to about <NUM>. In some embodiments, TTFields may include alternating fields <NUM> in the frequency range of about <NUM> to about <NUM>. In some embodiments, the TTFields may include alternating fields <NUM> in the frequency range of about <NUM> to about <NUM>. Fields <NUM> may be generated by a first electrode 14a connecting to the negative output of the electric field generator <NUM> and a second electrode 14b connected to the positive output. Microtubules <NUM>, as well as other polar macromolecules within the dividing cell <NUM> or surrounding the dividing cell <NUM>, may have strong dipole moment providing susceptibility to such TTFields <NUM>. Positive outputs of the microtubules <NUM> may be positioned at centrioles <NUM>. At least one negative pole may be positioned at a center <NUM> of the dividing cell <NUM> and at least one negative pole may be positioned at a point of attachment <NUM> of the microtubules <NUM> to a cell membrane <NUM> of the dividing cell <NUM>. The locations of the positive outputs and the negative outputs form at least one set of double dipoles. The at least one set of double dipoles may provide susceptibility to TTFields <NUM> of differing directions. As used herein, the alternating electric field may be referred to as the electric field or the TTField <NUM>. The TTField <NUM> may be a frequency specific, alternating electric field that is applied to the site of a tumor in the body. In some embodiments, one or more electrical fields may be applied to the dividing cell <NUM> in order to increase the permeability of the membrane of the dividing cell <NUM>. For example, one or more electrical fields may be applied to the dividing cell <NUM> in order to increase the permeability of the membrane of the dividing cell <NUM> such that one or more chemicals, drugs, DNA and/or chromosomes may be introduced into the dividing cells (i.e., via electroporation).

<FIG> illustrates a schematic diagram of an exemplary electronic apparatus <NUM> configured to generate TTFields <NUM> in accordance with the present disclosure. The TTFields <NUM> described may be capable of destroying one or more tumor cells. The specifications of the electronic apparatus <NUM> as a whole and/or individual components of the electronic apparatus <NUM> as described herein may be influenced by living systems behaving according to "Ohmic' properties, rather than dielectric properties, at the frequency of the TTFields (e.g., <NUM>-<NUM> or <NUM> -<NUM>).

Generally, the electronic apparatus <NUM> may include an electric field generator <NUM> and two or more conductive leads <NUM>. For example, in <FIG>, the electronic apparatus includes a first conductive lead 34a and a second conductive lead 34b. The first conductive lead 34a includes a first end 36a and a second end 40a. The first end 36a of the first conductive lead 34a is conductively attached to the electric field generator <NUM> and the second end 40a of the first conductive lead 34a is connected to a first pad 42a. Similarly, the second conductive lead 34b includes a first end 36b and a second end 40b. The first end 36b of the second conductive lead 34b is conductively attached to the electric field generator <NUM> and the second and 40b of the second conductive lead 34b is connected to a second pad 42b. The first pad 42a and the second pad 42b may also be referred to as electrodes, such as the first electrode 14a or the second electrode 14b, or electrode pad.

The electric field generator <NUM> is configured to provide one or more electric signals (TTFields signals) in the shape of waveforms and/or trains of pulses as an output. Each pad 42a and 42b are provided with a potential difference by the electric signals (e.g., waveforms) that generate a current when the pads 42a and 42b are attached to a body by the electric signals (e.g., wave forms). As each of the first pad 42a and the second pad 42b is provided with the electric signals having a frequency and an amplitude, an electrical current will flow between the first pad 42a and the second pad 42b when the first pad 42a and the second pad 42b are applied on a conductive material, such as a human body.

The electric field generator <NUM> may be configured to generate an alternating voltage wave form at frequencies in the range from about <NUM> to about <NUM>, and ranges within (i.e., from about <NUM> to about <NUM>, from about <NUM> to about <NUM>). In some embodiments, the electric field generator <NUM> is configured to generate an alternating voltage wave form at frequencies in the range of about <NUM> to about <NUM> (i.e., the TTFields). The voltages are such that an electric field intensity in tissue within the treatment area is in the range of about <NUM> V/cm to about 10V/cm, To achieve this field, the potential difference between the two conductors <NUM>, (i.e. electrode element <NUM> described in detail below and shown in <FIG>) in each of the first pad 42a or second pad 42b may be determined by the relative impedances of the body.

In some embodiments, the first pad 42a and the second pad 42b may be configured to generate an alternating electric field within a target region of a patient. The target region may comprise, for example, at least a portion of a tumor. Generation of the alternating electric field may be configured to selectively destroy and/or inhibit growth of at least a portion of the tumor. The alternating electric field may be generated at any frequency capable of selectively destroying and/or inhibiting growth of at least a portion of the tumor. For example (but not by way of limitation), the alternating electric field may have a frequency within the range of about <NUM> to about <NUM>, as well as a range formed from any values within (i.e., a range of from about <NUM> to about <NUM>, a range of from about <NUM> to about <NUM>, a range of from about <NUM> to about <NUM>, etc.), and a range that combines two integers that fall between two of the above-referenced values (i.e., a range of from about <NUM> to about <NUM>, a range of from about <NUM> to about <NUM>, etc.).

In some embodiments, the alternating electric field may be configured to be imposed at two or more different frequencies. In some embodiments, each of the two or more different frequencies may be selected from any of the above-referenced values, or a range formed from any of the above-referenced values, or a range that combines two integers that fall between two of the above-referenced values.

In some embodiments, the first pad 42a and the second pad 42b (i.e., a pair of pads) may be configured differently depending upon the application in which the pair of pads 42a and 42b are to be used. In some embodiments, the pair of pads 42a and 42b may be externally applied to a patient (e.g., applied to an epidermis layer of skin of a patient) with the generation of the electric field (TTField) provided within tissue of the patient. Generally, each of the first pad 42a and the second pad 42b is placed on the epidermis of the skin of the patient by a user such that the electric field is configured to generate across tissue of a patient within a predetermined treatment area. TTFields that are applied externally can be of a local type or widely distributed type, for example, the treatment of skin tumors and treatment of lesions close to the skin surface.

In some embodiments, the user may be a medical professional, such as a doctor, nurse, therapist, or other person acting under the instruction of a doctor, nurse, or therapist. In some embodiments, the user may be the patient, that is, the patient may place the pads 42a and 42b on the epidermis layer within a predetermined treatment area.

In some embodiments, the electronic apparatus <NUM> may optionally include a control box <NUM> and one or more temperature sensor <NUM> coupled to the control box <NUM>. In some embodiments, multiple temperature sensors <NUM> may be positioned to sense temperature at the predetermined treatment area. The one or more temperature sensor <NUM> may include, but are not limited to, thermistors, thermocouples, RTDs, integrated circuit temperature sensors such as the Analog Devices AD590 and the Texas Instruments LM135, and/or combinations thereof. It is contemplated that any temperature sensor <NUM> known within the art may be used if configured to provide an accurate and/or precise temperature reading of the predetermined treatment area. The control box <NUM> may be configured to control amplitude of the electric field so as not to generate excessive heating in the treatment area.

In some embodiments, the control box <NUM> may be configured to control output of the electric field generator <NUM>. For example, in some embodiments, the control box <NUM> may be configured to control output of the electric field generator <NUM> such that output remains constant at a value preset by a user. In some embodiments, the control box <NUM> may be configured to set output of the electric field generator <NUM> at a maximal value, with the maximal value configured such that excessive heat is not provided at the predetermined treatment area. In some embodiments, the control box <NUM> may be configured to provide one or more feedback indicators. For example, the control box <NUM> may be configured to provide a feedback indicator (e.g., sound, light) when a temperature of the predetermined treatment area (as sensed by temperature sensor <NUM>) exceeds a preset limit.

In some embodiments, the control box <NUM> may be configured to control output of the electric field generator <NUM> based on one or more readings of the temperature sensor <NUM>. In some embodiments, one or more temperature sensor <NUM> may be connected to and/or otherwise associated with the first pad 42a or the second pad 42b and configured to sense temperature of the epidermis and/or treatment area at either one or both of the first pad 42a or the second pad 42b.

In some embodiments, one or more of the conductive leads <NUM> may be standard isolated conductors having a flexible metal shield. In some embodiments, the flexible metal shield may be grounded to prevent spread of any electric field generated by the one or more conductive leads <NUM>.

Pads 42a and 42b may be shaped, sized and positioned to generate the TTField configuration, direction and intensity at the treatment area. To that end, the pads 42a and 42b may be square, rectangular, circular, oval, or any fanciful shape.

<FIG> depict a first embodiment of a transducer array <NUM> incorporating the pads 42a and 42b. The pads 42a and 42b are referred to below as "electrode elements. " The transducer array <NUM> is also referred to herein as an "electrode apparatus" with a first layout of electrode elements, with <FIG> being an exploded or assembly view showing all of the various components and their arrangement relative to each other. <FIG> show the individual components in greater detail.

One of the components that defines the configuration of the transducer array <NUM> is the flex circuit <NUM> (<FIG> and <FIG>), which may be made with electrical traces extending along the branches of the flex circuit <NUM> as is well known in the art. The flex circuit <NUM> has a branching or ramified configuration. There is a central trunk 108a-<NUM> that extends in a longitudinal direction. There are also a plurality of branches that extend laterally from both sides of the trunk 108a-g of the flex circuit <NUM>. In some embodiments (including the embodiments depicted in <FIG>, <FIG>, and <FIG>), these branches are perpendicular to the longitudinal direction and are arranged as rows 106a-106e of the flex circuit <NUM>. In the illustrated embodiment, each of the rows 106a-e of the flex circuit <NUM> includes two branches - one on either side of the trunks 108a-<NUM>. The proximal end of each branch is connected to and extends from the trunk 108a-g of the flex circuit <NUM>, while the distal end of each branch remains free. Advantageously, this configuration improves the flexibility of the flex circuit <NUM>, and reduces tensile stresses applied on the transducer array <NUM> by skin movement (bending, stretching, twisting, breathing, etc.), thereby improving and prolonging adhesion of the transducer array <NUM> to the skin. The transducer array <NUM> also improves user comfort and reduces skin damage. Note that in the embodiment illustrated in <FIG> and <FIG>, the trunk 108a-<NUM> shifts back and forth in segments between successive rows of the flex circuit <NUM>. In these embodiments, only some of the segments 108a, 108c, 108e, and <NUM> extend in the longitudinal direction, and those longitudinal segments are interconnected by additional segments 108b, 108d, and 108f that extend in the lateral direction. As a result, in these embodiments, the trunks 108b, 108d, and 108f shift back and forth in the lateral direction as the trunks 108a, 108c, 108e and <NUM> extend in the longitudinal direction. In alternative embodiments, the trunk is straight.

The flex circuit <NUM> includes a number of mounting pads <NUM> arranged along the rows 106a-106e. A number of electrode elements <NUM> (<FIG> and <FIG>) - for example, twenty as shown in the <FIG> embodiment for a typically sized adult male - are disposed on the inner (i.e., skin-facing) side of the mounting pads <NUM> of the flex circuit <NUM> (shown in <FIG> and <FIG>) with an electrically conductive connection between each of the electrode elements <NUM> and the flex circuit <NUM>. The electrode elements <NUM> may be on the order of <NUM> thick and <NUM> in diameter and may optionally be slightly smaller in diameter than the mounting pads <NUM>. Each of the electrode elements <NUM> may be formed from a circular conductive plate that is coated with a ceramic dielectric material as is known in the art, and the circular conductor is electrically connected to an electrical contact of the flex circuit <NUM>. The ceramic dielectric material faces toward the patient's body so that the ceramic dielectric material can make contact with the patient's skin (preferably via an intervening layer of hydrogel, as described below). The dielectric material may be a ceramic material, a non-flexible polymer, or a flexible polymer film.

The electrode elements <NUM> are provided with an outer side 111a and an inner side 111b. Only one of the electrode elements <NUM> is labeled with the reference numerals 111a and 111b for purposes of brevity. A corresponding number of stiffeners <NUM> (<FIG> and <FIG>) may optionally be attached to the outer side 111a of the mounting pads <NUM> of the flex circuit <NUM> generally opposite the electrode elements <NUM> attached to the inner side 111b. The stiffeners <NUM> may be on the order of <NUM> thick and may be slightly smaller in diameter than the mounting pads <NUM>. The stiffeners <NUM> may be made from any suitable material (e.g., a stiff, nonconductive plastic). In general, the stiffeners <NUM> help prevent the electrode elements <NUM> from breaking, given the flexible nature of the flex circuit <NUM> and the thin, fragile nature of the ceramic dielectric used for the electrode elements <NUM>.

In some embodiments, each of the electrode elements <NUM> has a corresponding disc of conductive gel element <NUM> (<FIG>, <FIG>, and <FIG>) disposed on the inner side 111b of the electrode element <NUM>, to establish good electrical conductivity with the patient's skin. In some embodiments, the conductive gel element <NUM> is slightly larger in diameter than the electrode element <NUM>. The material is preferably gamma sterilization-compatible. For example, the conductive gel element <NUM> may be a hydrogel made from AG625, which is available from Axelgaard, with a thickness on the order of <NUM> micrometers, and with a volume resistivity of <NUM> ohm-cm max. In some embodiments, the conductive gel element <NUM> includes one or more conductive gel layer <NUM> (see <FIG>).

In some embodiments, the electrode array includes a conductive gel assembly <NUM>, including one or more conductive gel element <NUM> and a support layer <NUM> connected to the one or more conductive gel element <NUM>. The conductive gel element <NUM> includes one or more conductive gel layers <NUM> that may be prefabricated prior to inclusion on the electrode elements <NUM>. In some embodiments, one or more conductive gel layers <NUM> may be applied in liquid form onto the electrode elements <NUM> and then cured (e.g., UV curing, electron beam curing) directly on the electrode element <NUM> and/or other portion of the transducer array <NUM>. The support layer <NUM> can be applied to cover the conductive gel layer <NUM> and the one or more electrode elements <NUM>, and another amount of conductive gel in liquid form or cured form may be applied to the support layer <NUM> so that the conductive gel layers <NUM> forming one of the conductive gel elements <NUM> are aligned and sandwich the support layer <NUM>. In some embodiments, one or more conductive gel layers <NUM> may be cured directly on the support layer <NUM>, for example and then subsequently applied to the electrode elements <NUM>. The support layer <NUM> includes a first side 115a and a second side 115b. The support layer <NUM> is sized and dimensioned to extend over one or more electrode elements <NUM>. The conductive gel layer 106a is disposed upon and attached to the first side 115a of the support layer <NUM>. The conductive gel layer 106b is disposed upon and attached to the second side 115b of the support layer <NUM>. The support layer <NUM> can be disposed on both of the first side 115a and the second side 115b to encapsulate a portion of the support layer <NUM> between the conductive gel layers 106a and 106b. The conductive gel assembly <NUM> can be manufactured separately from the other components of the transducer array <NUM> and subsequently connected to the transducer array <NUM>. Or, the conductive gel assembly <NUM> can be manufactured with the transducer array <NUM>, such as by forming the conductive gel layer(s) <NUM> on the electrode elements <NUM> either before or after application of the support layer <NUM> over the electrode elements <NUM>.

The bulk electron transport agent(s) may be any substance that is capable of enhancing the electrical and/or thermal conductivity of the conductive gel. In certain non-limiting embodiments, the bulk electron transport agent(s) includes one or more ionic compounds, one or more metals, or one or more non-metals, as well as any combinations thereof. In certain non-limiting embodiments, the bulk electron transport agent comprises an amorphous carbon and/or a crystalline carbon. Particular (but non-limiting) examples of bulk electron transport agents that may be utilized in accordance with the present disclosure include carbon black, graphene, and graphite.

In some embodiments, the conductive gel element <NUM> and/or the one or more conductive gel layer <NUM> are formed primarily of a conductive gel or semi-solid conductive gel such as described below. The conductive gel element <NUM> may be in any form that allows the electrode elements <NUM> to function in accordance with the present disclosure. For example (but not by way of limitation), the conductive gel element <NUM> may be in the form of a hydrogel or a hydrocolloid.

The conductive gel element <NUM> may have properties including, but not limited to, high conductivity, tackiness, and/or biocompatible for extended periods of time. For example, the conductive gel element <NUM> may include AG603 Hydrogel, available from AmGel Technologies, having a principle place of business in Fallbrook, California.

The conductive gel element <NUM> may be used with modified hydrogels, including but not limited to perforations, recesses, and/or protrusions. Such features are further disclosed in detail in <CIT>, entitled "Conductive Gel Compositions Comprising Bulk Electron Transport Agents and Methods of Production and Use Thereof".

In some embodiments, the conductive gel element <NUM> may be sterile. In some embodiments, the conductive gel element <NUM> may be configured such that the conductive gel element <NUM> does not substantially degrade upon exposure to sterilization conditions that include gamma rays or ethylene oxide gas, for example.

The conductive gel element <NUM> may be formed of any hydrophilic polymer that allows the conductive gel element <NUM> to function in accordance with the present disclosure. For example (but not by way of limitation), the conductive gel element <NUM> may be a polyacrylic acid gel, a povidone gel, or a cellulose gel. In addition, the conductive gel may comprise at least one of chitosan, alginate, agarose, methylcellulose, hyaluronan, collagen, laminin, matrigel, fibronectin, vitronectin, poly-<NUM>-lysine, proteoglycans, fibrin glue, gels made by decellularization of engineered and/or natural tissues, as well as any combinations thereof. Further, the conductive gel element <NUM> may comprise at least one of polyglycolic acid (PGA), polylactic acid (PLA), poly-caprolactone (PCL), polyvinyl alcohol (PVA), polyethylene glycol (PEG), methyl methacrylate, poly(methyl methacrylate) (PMMA), poly(<NUM>-hydroxyethyl methacrylate) (PolyHEMA), poly(glycerol sebacate), polyurethanes, poly(isopropylacrylamide), poly(N-isopropylacrylamide), or any combination thereof.

In some embodiments, the conductive gel element <NUM> may comprise one or more of the following chemical and structural features/properties: a polymer chain length in a range of from about <NUM> to about <NUM>; a pH in a range of from about <NUM> to about <NUM>; a volume resistivity of less than about <NUM> Ohm-in; a skin adhesion rate of at least about <NUM>/inch; and a thickness in a range of from about <NUM> mil to about <NUM> mil.

In some embodiments, the conductive gel element <NUM> may be optimized for use at body temperature (i.e., in a range of from about <NUM> to about <NUM>) for extended periods of time.

The polymer(s) of the conductive gel element <NUM> may be provided with any polymer chain length that allows the conductive gel element <NUM> composition(s) to function as described herein. For example (but not by way of limitation), the polymer chain length may be within the range of about <NUM>, to about <NUM>, and above, as well as a range that combines any two of the values within (i.e., a range of from about <NUM> to about <NUM>, a range of from about <NUM> to about <NUM>, or a range of from about <NUM> to about <NUM>, a range of from about <NUM> to about <NUM>, etc.), and a range that combines two integers that fall between two of the above-referenced values (i.e., a range of from about <NUM> to about <NUM>, etc.).

In some embodiments, the range of the polymer chain length may be dependent upon the frequency(ies) of the alternating electric field. For example (but not by way of limitation), the range of the polymer chain length may be based upon a range of frequencies of the alternating electric field. Non-limiting examples include a range of from about <NUM> to about <NUM> when the alternating electric field has a frequency in a range of from about <NUM> to about <NUM>, a range of from about <NUM> to about <NUM> when the alternating electric field has a frequency in a range of from about <NUM> to about <NUM>, etc..

The conductive gel element <NUM> may be provided with any pH that does not damage the skin of a patient. For example (but not by way of limitation), the conductive gel element <NUM> may have a pH of about <NUM>, about <NUM>, about <NUM>, about <NUM>, about <NUM>, as well as a range formed from any of the above values (i.e., a range of from about <NUM> to about <NUM>, a range of from about <NUM> to about <NUM>, etc.).

The conductive gel element <NUM> may be provided with any level of volume resistivity that maximizes the conductivity of the gel. For example (but not by way of limitation), the conductive gel element <NUM> may have a volume resistivity within a range of less than about <NUM> Ohm-in to less than about <NUM> Ohm-in, or lower, as well as a range formed of any of the above values within (i.e., a range of from about <NUM> Ohm-in to about <NUM> Ohm-in, etc.) and a range that combines two integers that fall between two of the above-referenced values (i.e., a range of from about <NUM> Ohm-in to about <NUM> Ohm-in, etc.).

The conductive gel element <NUM> may be provided with any skin adhesion rate that allows the conductive gel element <NUM> to function in accordance with the present disclosure. For example (but not by way of limitation), the skin adhesion rate of the gel may be within a range of at least about <NUM>/inch to at least about <NUM>/inch, or higher, as well as a range of any of the above values within (a range of from about <NUM>/inch to about <NUM>/inch, etc.), and a range that combines two integers that fall between two of the above-referenced values (i.e., a range of from about <NUM>/inch to about <NUM>/inch, etc.).

In some embodiments, the conductive gel element <NUM> may further include at least one additive. Any type of additive that allows the conductive gel element <NUM> to function in accordance with the present disclosure and that may optionally further enhance the conductivity and non-sensitizing properties of the conductive gel may be utilized in accordance with the present disclosure. Non-limiting examples of additives that may be utilized include at least one of a humectant, a preservative, an antibacterial agent, a vitamin, a moisturizer, or any combinations thereof, and the like.

The conductive gel element <NUM> may be provided with any concentration of one or more salts that allow gel compositions to function as described herein. The free salt concentration may be with the range of at least about <NUM> to about <NUM>, or higher, as well as any range that combines any two of the values within (e.g., range of about <NUM> to about <NUM>, a range of about <NUM> to about <NUM>).

The conductive gel assembly <NUM> may be provided with any thickness t<NUM> that allows the conductive gel element <NUM> to function in accordance with the present disclosure. Non-limiting examples of thicknesses t<NUM> that may be utilized in accordance with the present disclosure include a range of about <NUM> mil to about <NUM> mil, or higher, as well as a range that combines any two of the above-referenced values (i.e., a range of from about <NUM> mil to about <NUM> mil, etc.), and a range that combines two integers that fall between two of the above-referenced values (i.e., a range of from about <NUM> mil to about <NUM> mil, etc.).

In some embodiments, the conductive gel assembly <NUM> and the conductive gel element <NUM> may have a shelf life of at least about six months. For example (but not by way of limitation), the conductive gel element <NUM> has a shelf life of at least about <NUM> months or at least about <NUM> months.

The one or more support layers <NUM> may be provided within the conductive gel element <NUM> (as shown in <FIG>) or outside of the conductive element as shown in <FIG>. Generally, the one or more support layers <NUM> may be configured to provide reinforcement to the conductive gel element <NUM> to prevent lateral movement of the conductive gel element <NUM> when the conductive gel element <NUM> is applied to the skin of the patient. To that end, the one or more support layer <NUM> may provide strength and/or support to the one or more conductive layer <NUM> (e.g., conductive gel layers 106a and/or 106b). The one or more support layer <NUM> may be constructed of a woven or nonwoven material. In some embodiments, at least a portion of the one or more support layer <NUM> may include Reemay (i.e., spun nylon). In some embodiments, at least a portion or the entirety of the one or more support layer <NUM> may be constructed of a nonconductive material. In some embodiments, at least a portion or the entirety of the one or more support layer <NUM> may be constructed of a non-metal conductive material, such as carbon.

The support layer <NUM> may serve as an anchor between the conductive gel layer(s) <NUM> and one or more other components within the transducer array <NUM>, such as the electrode elements <NUM> or the flex circuit <NUM> by attaching the support layer to the electrode elements <NUM> or the flex circuit <NUM>, for example with a bond separate from any bond provided by the conductive gel layer(s) <NUM>. In some embodiments, at least a portion of the support layer <NUM> may extend between at least two components of the transducer array <NUM>, such as the electrode elements <NUM>, or the conductive gel elements <NUM>. For example, as illustrated in <FIG>, the support layer <NUM> extends between the electrode elements <NUM> and the conductive gel elements <NUM>. In some embodiments, the conductive gel elements <NUM> may be positioned such that each conductive gel element <NUM> is aligned with one electrode element <NUM>.

A gap may exist between each electrode element <NUM> such that each electrode element <NUM> is positioned at a distance from any adjacent electrode element <NUM>. To that end, the conductive gel in liquid form or semi-solid conductive gel forming the conductive gel layer 106a and/or 106b may be dispensed onto the support layer <NUM> at pre-determined particular locations during formation of the transducer array <NUM> (e.g., corresponding to a single electrode element <NUM>, corresponding to two electrode elements <NUM>, corresponding to multiple electrode elements <NUM>, and the like). In some embodiments, one or more dielectric materials may be positioned within the gap between adjacent isolated electrode elements <NUM>, for example.

Additionally, a ring-shaped hydrogel barrier <NUM> (<FIG>, <FIG>, <FIG> and <FIG>) is optionally provided, surrounding each of the conductive gel elements <NUM>. In general, the hydrogel barriers <NUM> help maintain the integrity of the conductive gel elements <NUM> throughout the duration of wear and prevent migration of the hydrogel from its correct location under the electrode elements <NUM>. The hydrogel barriers <NUM> may be made, e.g., from MED 5695R, available from Vancive Medical Technologies, which is a polyethylene foam, and may be single-coated with WetStickTM synthetic rubber adhesive, also available from Vancive Medical Technologies. The hydrogel barriers <NUM> may be <NUM> micrometers thick, and are preferably gamma sterilization-compatible.

To increase patient comfort, the transducer array <NUM> may optionally include a conformal foam layer <NUM> (<FIG> and <FIG>) positioned beneath the flex circuit <NUM>, and shaped to closely follow the branching configuration of the flex circuit <NUM>. Note that unlike the flex circuit <NUM> (which has solid circular mounting pads <NUM> for the electrode elements <NUM>), the foam layer <NUM> has ring-shaped regions <NUM> that surround the electrode elements <NUM> so as not to intervene between the electrode elements <NUM> and the patient's skin. A suitable thickness for the conformal foam layer <NUM> is on the order of <NUM>, and the foam layer <NUM> is preferably the same thickness as the electrode elements <NUM>. The foam layer <NUM> preferably covers the entire surface of the flexible flex circuit <NUM> (except for the regions where the electrode elements <NUM> are positioned) while maintaining overall flexibility and conformability of the transducer array <NUM>. But in alternative embodiments, the foam layer <NUM> only covers a portion of the surface of the flexible flex circuit <NUM>. In some embodiments, the size of the foam layer <NUM> may be minimized to the extent possible so as not to reduce the overall breathability and fluid-vaporizing properties of the transducer array <NUM>.

The conformal foam layer <NUM> may be made, e.g., from polyethylene foam such as MED 5696R available from Vancive Medical Technologies. The conformal foam layer <NUM> may be affixed to the flex circuit <NUM> using a suitable adhesive (e.g., WetStickTM synthetic rubber adhesive, also available from Vancive Medical Technologies). The foam layer <NUM> advantageously protects the patient from potentially sharp edges of the conductive traces on the flex circuit <NUM>. This is particularly important in the context of flexible transducer arrays because flexing the transducer arrays <NUM> can cause the flat conductive traces to twist, which can cause the potentially sharp edges of those conductive traces to tilt down towards the patient's skin. Notably, interposing the foam layer <NUM> between the conductive traces of the flex circuit <NUM> and the patient's skin protects the patient from cuts and/or pain that might be caused by those potentially sharp edges.

The transducer array <NUM> also includes a skin-level layer of adhesive 118a disposed beneath the foam layer <NUM>, as shown in <FIG>, <FIG>, and <FIG>. (The skin-level adhesive 118a also appears in <FIG>. ) In general, the skin-level layer of adhesive 118a follows the branching configuration of the flex circuit <NUM> and the foam layer <NUM>, but with the various branches and trunk portions of the skin-level adhesive 118a being slightly wider than the corresponding portions of the flex circuit <NUM> and the foam layer <NUM> so as to at least partially overlap with the spaces between the branches of the flex circuit <NUM> and the foam layer <NUM>. Notably, the skin-level adhesive 118a includes cutouts 120a along the branches of the adhesive, and cutouts 120b at the free ends of the branches of the adhesive. These cutouts 120a, 120b are shaped so as not to intervene between the electrode elements <NUM> or the conductive gel elements <NUM> and the patient's skin. The skin-level layer of adhesive 118a also functions as a constructive element, to stabilize the central area around the electrode elements <NUM> to prevent movement of the electrode elements <NUM> relative to the patient's skin.

The skin-level layer of adhesive 118a may be made from a polyester/rayon-blend, spunlace non-woven tape material such as <NUM>® <NUM>, which is <NUM> micrometers thick. The tape may be double-coated with acrylate adhesive, to provide a peel strength on the skin-facing side (e.g., <NUM> lbf/inch) and a higher peel strength (e.g., <NUM> lbf/inch) on the opposite, outer side. The material is preferably hypoallergenic, highly conformable, and breathable; with a high moisture vapor transmission rate; and it is preferably gamma sterilization-compatible. To prevent excessive sweating and moisture from being trapped under the transducer array <NUM>, the overall surface area of the skin-level layer of adhesive 118a may be minimized, e.g., by making it just slightly wider than the corresponding portions of the flex circuit <NUM> and the foam layer <NUM>.

Note that in embodiments where a conformal foam layer <NUM> is omitted, the layer of adhesive 118a may be connected directly to the flex circuit <NUM> with no intervening components disposed therebetween. Alternatively, in those embodiments where the conformal foam layer <NUM> is provided, the layer of adhesive <NUM> may be connected indirectly to the flex circuit <NUM>, with a foam layer <NUM> disposed therebetween. In these embodiments, the foam layer <NUM> may be connected to the flex circuit <NUM> with a bonding material, such as an adhesive or a cohesive.

An exemplary embodiment of the support layer <NUM> is shown in <FIG> and <FIG>. The support layer <NUM> (<FIG>, <FIG>, and <FIG>) is positioned below and connected to an inner side of the flex circuit <NUM>, the inner side 111b of the electrode elements <NUM> or combinations thereof. The support layer <NUM> has a number of slots <NUM>, which divide the support layer <NUM> into a number of separate fingers <NUM>, each of which is underneath a respective branch of the flex circuit <NUM>. The support layer <NUM> is provided with <NUM> slots 123a-h, and <NUM> fingers 124a-j. The slots 123a-h are preferably significantly narrower than the fingers 124a-j and the fingers 124a-j are preferably wider than the diameters of the electrode elements <NUM>. This configuration results in the fingers 124a-j of the support layer <NUM> overlapping with the spaces between the branches of the flex circuit <NUM>. The transducer array <NUM> may also be provided with an adhesive layer 118b positioned between the support layer <NUM> and the flex circuit <NUM> to anchor the support layer <NUM> to the flex circuit <NUM>. The fingers 124a-j overlie and extend between the conductive gel elements <NUM>. The fingers 124a-j are connected to the conductive gel elements <NUM> and serve to provide lateral support for the conductive gel elements <NUM> so as to prevent the conductive gel elements <NUM> from moving laterally when the conductive gel elements <NUM> are applied to the skin of the patient. The flexible nature of the support layer <NUM> allow the fingers 124a-j to move independently of each other as the branches of the flex circuit <NUM> move independently of each other. This, in turn, helps to maintain conformability of the transducer array <NUM> and adhesion to the patient's skin even as the patient moves.

A top, covering adhesive-backed layer <NUM> (<FIG>, <FIG>, and <FIG>) is positioned above and connected to an outer side of the flex circuit <NUM>. The covering adhesive-backed layer <NUM> has a number of slots <NUM>, which divide the covering adhesive-backed layer <NUM> into a number of separate fingers <NUM>, each of which overlies a respective branch of the flex circuit <NUM>. The slots <NUM> are preferably significantly narrower than the fingers <NUM> and the fingers <NUM> may be wider than the diameters of the electrode elements <NUM>. This configuration results in the fingers <NUM> of the covering adhesive-backed layer <NUM> overlapping with the spaces between the branches of the flex circuit <NUM> to provide maximal adhesion of the covering adhesive-backed layer <NUM> to the patient's skin around the electrode elements, while still allowing the fingers <NUM> of the covering adhesive layer to move independently of each other as the branches of the flex circuit <NUM> move independently of each other. This, in turn, helps to maintain conformability of the transducer array <NUM> and adhesion to the patient's skin even as the patient moves. In addition, the covering adhesive-backed layer <NUM> preferably extends beyond the perimeter of the flex circuit <NUM> to provide additional adhesion to the skin at the outer boundary of the transducer array <NUM>.

The covering adhesive-backed layer <NUM> may be made from <NUM>® <NUM>, which is a <NUM>% polyester, spunlace non-woven tape, for example. This material may be single-coated with acrylate adhesive on the skin-facing side, which adheres the covering adhesive-backed layer <NUM> to the outer surface of the flex circuit <NUM>. The material forming the covering adhesive-backed layer <NUM> may have a thickness of <NUM> micrometers. The covering adhesive-backed layer <NUM> may be hypoallergenic, highly conformable, breathable, and/or gamma sterilization-compatible.

As shown in <FIG>, the support layer <NUM> may be shaped to be within the confines of the layer <NUM>. Further, the support layer <NUM> may be shaped so that the fingers <NUM> of the support layer underlie and are aligned with fingers <NUM> of the layer <NUM> so that the fingers <NUM> move with the fingers <NUM>.

Shown in <FIG> is a bottom plan view of a portion of the transducer assembly <NUM> depicting the support layer <NUM> adhered to the flex circuit <NUM>, and positioned between the conductive gel element <NUM> and the flex circuit <NUM>. In some embodiments, the transducer array <NUM> can be made by attaching the support layer <NUM> to the flex circuit <NUM> such that the electrode elements <NUM> are between the support layer <NUM> and the flex circuit <NUM>. In this position, the conductive gel elements <NUM> can be applied in liquid form to the support layer <NUM> directly over the electrode elements <NUM> and then cured. In this embodiment, at least some of the liquid forming the conductive gel elements <NUM> may pass through the support layer <NUM> thereby forming the layers 106a and 106b encapsulating the support layer <NUM> in the conductive gel elements <NUM> when cured. Further, the conductive gel elements <NUM>, when cured, may adhere to the electrode elements <NUM> thereby providing further lateral support to the conductive gel elements <NUM> separate from the adhesive layer 118b attaching the support layer <NUM> to the flex circuit <NUM>. In some embodiments, the support layer <NUM> can be anchored to the flex circuit <NUM> in a manner other than an adhesive. For example, a mechanical linkage such as thread, staple or rivet can be used to connect the support layer <NUM> to the flex circuit <NUM>.

Notably and advantageously, two separate factors contribute to the adhesion of the entire transducer array <NUM> to the patient's skin. The first factor is the portions of the lower surface of the top adhesive layer <NUM> that contact the skin through the spaces between the branches of the flex circuit <NUM> and beyond the perimeter of the flex circuit <NUM>. The second factor is the layer of adhesive 118a disposed between the foam layer <NUM> and the person's skin (or, between the flex circuit <NUM> and the person's skin in those embodiments that do not include the foam layer <NUM>). The inclusion of these two separate adhesive components provides significantly improve adhesion of the transducer array <NUM> to the patient's skin. This feature of the transducer array <NUM> enhances the degree of adhesion of the transducer array <NUM> to the patient's skin around the electrode elements, resulting in prolonged and better skin/electrode contact as compared to configurations in which the only adhesion was provided by an adhesive-backed patch overlying the entire transducer array.

In some embodiments, the covering adhesive-backed layer <NUM> includes a central aperture <NUM> and a slit <NUM> extending from the innermost end <NUM> of one of the slots <NUM> - in particular, the innermost slit-end that is closest to the central aperture <NUM>. The central aperture <NUM> permits an electrical cable <NUM> (shown in <FIG>) that protrudes from the back surface of the flex circuit <NUM> to extend through the covering adhesive-backed layer <NUM>. This electrical cable <NUM> is used to connect the flex circuit <NUM> to a TTFields therapy controller (not illustrated) via a connector. The slit <NUM> is useful for positioning the adhesive-backed layer <NUM> over the flex circuit <NUM> after the cable <NUM> has been connected to the flex circuit <NUM> during the assembly process. In particular, portions of the covering adhesive-backed layer <NUM> can be moved away from each other to open the slit <NUM>, such that the covering adhesive-backed layer <NUM> can be passed around the electrical cable <NUM> on either side and then the entire adhesive-backed layer can be pressed into proper position.

Once the transducer array <NUM> has been properly attached to the patient's skin with the covering adhesive-backed layer <NUM> securing the transducer array <NUM> in place, the central aperture <NUM> may be covered, for protection, with a top adhesive-backed slot-cover <NUM> (<FIG>, <FIG>). The slot-cover <NUM> may be a disc-shaped item, formed from the same material and in the same manner as the covering adhesive-backed layer <NUM>. In some preferred embodiments, the slot cover <NUM> includes a slot <NUM> for the electric cable <NUM> to pass through.

In some embodiments, the entire assembly of components described above is protected, prior to use on a patient, with a two-part release liner <NUM> (<FIG> and <FIG>). The release liner <NUM> has an overall shape that generally follows, but may be slightly larger than, the outer periphery of the covering adhesive-backed layer <NUM>. It may be made from, for example, AR W4000, available from Adhesive Research, which is a white, silicone-coated PET (polyethylene terephthalate) material that is <NUM> micrometers thick.

In the <FIG> embodiment of a transducer array <NUM> described above, there are <NUM> electrode elements arranged in five rows, with two, five, six, five, and two electrode elements in each of the successive rows. (The rows correspond with the branches of the flex circuit <NUM> and are perpendicular to the longitudinal direction in which the trunk <NUM> extends. Thus, the rows are oriented horizontally and the trunk <NUM> is oriented vertically as the transducer array <NUM> is oriented in <FIG> and the flex circuit <NUM> is oriented in <FIG>. ) Depending on factors such as the size, sex, age, etc. of a patient, however, there could be more or less electrode elements <NUM> arranged in different configurations, while still adhering to the inventive concepts disclosed herein.

In both the <FIG> embodiment, the flex circuit <NUM> has a plurality of branches extending on each lateral side of the trunk region. But in alternative embodiments, the branches may be present only on a single lateral side of the trunk region (in which case, the trunk region would be located near one edge of the apparatus.

In some embodiments (including but not limited to the <FIG> embodiment) the flex circuit <NUM> is configured so that no more than three paths emanate from any given intersection on the flex circuit <NUM>. For example, in <FIG>, one path of the flex circuit <NUM> emanates from the intersections at the mounting pads 104a, two paths of the flex circuit <NUM> emanate from the intersections at the mounting pads 104b, and three paths of the flex circuit emanate from the intersections at the mounting pads 104c. Notably, there are no intersections on the flex circuit <NUM> from which more than three paths emanate. This holds true for both the intersections that are positioned at the mounting pads <NUM>, and also for intersections that are not positioned at one of the mounting pads <NUM> (e.g., The T-shaped intersections <NUM>).

In some embodiments, including the <FIG> embodiments, all segments of the flex circuit <NUM> are straight.

In some embodiments, including the <FIG> embodiments, an electrical cable terminates on the flex circuit <NUM> (as best seen in <FIG>). Optionally, in these embodiments, (as best seen in <FIG>) segments of the flex circuit <NUM> near the distal end of each branch are thinner than at least some of the segments of the flex circuit <NUM> that are adjacent to the location where the electrical cable terminates (e.g., segment 108d). This configuration increases the flexibility of the flex circuit, which also contributes to improving the flexibility of the entire apparatus.

<FIG> illustrates a flow chart <NUM> of an exemplary method of forming the exemplary conductive gel elements <NUM> in accordance with the present disclosure. In a step <NUM>, the support layer <NUM> may be positioned on and optionally anchored to the electrode elements <NUM> and the flex circuit <NUM>. In a step <NUM>, conductive gel (in liquid form) or semi-solid conductive gel may be dispensed in a predetermined pattern on at least a portion of the support layer <NUM> and cured (e.g., UV curing, electron beam curing) to form the conductive gel elements <NUM>. In forming the conductive gel elements <NUM>, the conductive gel or semi-solid conductive gel may be dispensed at one or more pre-determined targeted locations onto the electrode elements <NUM>. The electrode elements <NUM> may be provided in a predetermined pattern, and have a predetermined size. In these embodiments, the pre-determined targeted locations where conductive gel will be dispensed may correspond to the predetermined pattern and predetermined size of the electrode elements <NUM> so that when the conductive gel elements <NUM> are installed on the electrode elements <NUM>, the conductive gel elements <NUM> each correspond to at least one electrode element <NUM>.

In some embodiments, a mold and/or spacer may be used to provide for dispensing of the conductive gel (in liquid form) or semi-solid conductive gel at the one or more pre-determined targeted locations. For example, <FIG> illustrates an exemplary mold <NUM> disposed on a surface <NUM> of the electrode element <NUM>. The electrode element <NUM> includes a conductive material layer <NUM> and a polymer layer <NUM>. Generally, the mold <NUM> may be positioned prior to applying conductive gel element <NUM> (in liquid form) thereto. A sidewall <NUM> of the mold <NUM> may extend beyond the electrode element <NUM> and define a thickness for the semi-solid conductive gel element <NUM>. Alternatively, the mold <NUM> may be sized and shaped to accept both the electrode element <NUM> and the conductive gel element <NUM>. In this example, the electrode element <NUM> may be first disposed within the mold <NUM>, with the mold <NUM> having a sidewall height greater than height of the electrode element <NUM>, such that a portion of the sidewall <NUM> of the mold <NUM> that extends beyond the electrode element <NUM> defines a thickness for the semi-solid conductive gel element <NUM> produced thereon. The conductive gel element <NUM> may be then cured via a radiation source <NUM> (e.g., UV curing) such that the mold <NUM> provides boundaries and wall height equal to a pre-determined thickness desired for the conductive gel element <NUM>. The curing provides the polymerized conductive gel element <NUM>. In some embodiments, the conductive gel elements <NUM> may have a surface area that overlaps about <NUM>% to <NUM>% of the surface area of the particular electrode element <NUM>. In some embodiments, the conductive gel elements <NUM> may have a surface area that overlaps about <NUM>% to <NUM>% of the surface area of the particular electrode element <NUM>.

Curing the conductive gel element <NUM> directly on the electrode element <NUM> allows for in-line processing. <FIG> depicts in-line processing of multiple elements <NUM> or arrays <NUM> using a mold 500a that contacts first surfaces 502a, 502b and 502c of three separate electrode elements <NUM>. It should be noted that production for any number of elements <NUM> or arrays in batch or continuous format is contemplated.

In some embodiments, a quartz plate <NUM> (see <FIG>) may optionally be used during curing. The quartz plate <NUM> may be disposed on the liquid or semi-solid conductive gel element <NUM> applied to the surface <NUM> of the electrode element <NUM> prior to curing. The quartz plate <NUM> may be retained on the conductive gel element <NUM> during a portion or all of the curing step. The optional use of the quartz plate <NUM> may transfer radiation (e.g., UV light) therethrough providing homogeneous thickness of the polymerized conductive gel element <NUM>.

Referring to <FIG>, in some embodiments, one or more barriers <NUM> may be applied to the surface 502d of the electrode element <NUM> to maintain the conductive gel element <NUM> on the electrode element <NUM>. The barrier <NUM> may be formed of any material configured to be attached to the surface 502d of the electrode element <NUM> and maintain a perimeter sidewall and receiving space for the conductive gel element <NUM>. When the barrier <NUM> is formed of a polymer or other porous material (such as, but not limited to, MED 5695R, available from Vancive Medical Technologies, a polyethylene foam), the conductive gel element <NUM> may penetrate into the barrier <NUM> prior to curing and increase adhesion between the conductive gel element <NUM> and the electrode element <NUM>. Further, when the barrier <NUM> is formed of a polymer, the conductive gel element <NUM> may crosslink to the polymer of the barrier <NUM> during curing and yet further increase the adhesion between the conductive gel element <NUM> and the electrode element <NUM>. Barriers <NUM> may be similar to hydrogel barriers <NUM> shown in <FIG>, <FIG>, <FIG> and <FIG>.

The barrier <NUM> can be utilized with electrodes of any structure/configuration and produced from any material(s) as described herein. The use of hydrogel barriers can be particularly advantageous when a ceramic electrode is utilized (or when at least the surface on which the liquid hydrogel is disposed is formed of a ceramic material), as the hydrogel cannot crosslink to the ceramic; in this embodiment, the hydrogel barrier serves as to anchor the hydrogel to the electrode and prevent migration of the hydrogel from its correct location on the electrode.

In some embodiments, the electric field generator <NUM>, connected to the transducer array <NUM>, may supply a first electric signal having a first power and a first frequency to a first group of one or more electrode elements <NUM> at a first instance in time to generate a first TTField. The electric field generator <NUM>, at a second instance in time, may supply a second electric signal having a second power, the same as or different from the first power, and a second frequency, the same as or different from the first frequency, to a second group of electrode elements <NUM> to generate a second TTField. The first TTField and the second TTField may target the same target area or may target different target areas. In one embodiment, the first instance in time and the second instance in time may overlap, that is, the electric field generator <NUM> may supply the second electric signal to the second group while also supplying the first electric signal to the first group. In such an embodiment, the first group and the second group may be mutually exclusive.

In some embodiments, the electric field generator <NUM>, connected to the transducer array <NUM>, may supply a first electrical signal having a first power and a first frequency to a first group of one or more electrode element <NUM> and supply a second electrical signal having a second power and a second frequency to a second group of electrode elements <NUM> at the same instance in time. That is, the electric field generator <NUM> may simultaneously supply the first electric signal to the first group and the second electric signal to the second group. While the above embodiments describe only the first group and the second group, it is understood that there may be more than two groups. In one embodiment, the number of groups is dependent on the number of combinations of the conductive regions 56a-h.

Referring again to <FIG>, in some embodiments, leads 34a and 34b may include a DC blocking component, such as blocking capacitors 160a and 160b. Blocking capacitors may be operable to block DC current from passing to the pads 42a and 42b. The blocking capacitors 160a and 160b pass AC voltage to the pads 42a and 42b, and may be operable to prevent DC voltage or DC offset generated by the electric field generator <NUM> or otherwise present in the electrical signal from passing to or through the patient. In some embodiments, the blocking capacitors 160a and 160b may be non-polarized capacitors. In some embodiments, the blocking capacitors 160a and 160b may have a capacitance of about 1µF. In some embodiments, the blocking capacitor is a "Goldmax, <NUM> Series, Conformally Coated, X7R Dielectric, <NUM>-<NUM> VDC (Commercial Grade)" leaded non-polarized ceramic capacitor by KEMET Electronics Corporation (Fort Lauderdale, FL).

In some embodiments, the blocking capacitors 160a and 160b may be a component of the leads 34a and 34b, or an additional component at any position between the electrode element <NUM> of the first pad 42a and second pad 42b and the electric field generator <NUM>. For example, the blocking capacitors 160a and 160b may be intermediate the first end 36a of the second conductive lead 34b and the electric field generator <NUM>, or intermediate the second end 40b of the second conductive lead 34b and the second pad 42b. In some embodiments, one or more blocking capacitor 160a and 160b may be provided remote from the pads 42a and 42b. For example, one or more blocking capacitors 160a and 160b may be located on a non-patient side of the electrode element <NUM>.

Certain non-limiting embodiments of the present disclosure are related to kits that include components of the TTField generating systems, such as the electronic apparatus <NUM>, described herein. In some embodiments, one or more of the pad 42a and 42b, or transducer array <NUM> may be packaged as part of a kit. In some embodiments, the kit may include the first pad 42a and the lead 34a connected to the electrode elements <NUM>. In some embodiments, the kit may include the first pad(s) 42a and second pad(s) 42b, the transducer array <NUM> and the leads 34a and 34b. In some embodiments, the lead 34a may be mechanically coupled to the first pad 42a, and the second conductive lead 34b may be mechanically coupled to the second pad 42b, for example, by a rivet, by solder, by adhesive, by welding, and/or other electrically conductive coupling means. In some embodiments, the kit may further include the blocking capacitor(s) 160a or 160b positioned such that the electric signal passes through the blocking capacitor 160a or 160b.

Referring now to <FIG>, shown therein is a flow chart <NUM> of an exemplary method of using the electronic apparatus <NUM> and the transducer array <NUM> to apply a TTField to a patient. In a step <NUM>, the transducer array <NUM> may be attached to the skin of a patient. For example, electrode elements <NUM> may be attached to the skin of the patient on opposite sides of a tumor. In the context of a brain tumor, electrodes <NUM> may be positioned in the center of a person's head. For example, one of the electrode elements <NUM> may be positioned on the right side of the person's head, and another one of the electrode elements <NUM> may be positioned on the left side of the person's head. One or more electrode elements <NUM> may be applied to the patient's skin by a user.

In a step <NUM>, an AC voltage is applied between the electrode elements <NUM>. For example, the electric field generator <NUM> provides an alternating electric field having a frequency in a range of from about <NUM> to about <NUM> for a period of time to the electrode elements <NUM> applied to the patient to deliver TTF fields to the patient. In some embodiments, a user may initiate generation of the electric field generator <NUM> via the control box <NUM>. In some embodiments, application of the AC voltage may be performed more than one time in the period of time. Duration of multiple instances of application of AC voltage may be similar or different. In some embodiments, a time period of non-application of AC voltage may be between application of AC voltage.

<FIG> is a partial schematic view of the transducer array <NUM> constructed in accordance with the present disclosure. <FIG> is a cross-sectional view taken across one of the electrode elements <NUM>. The electrode element <NUM> includes a conductive plate <NUM> and a dielectric material <NUM> positioned adjacent to and covering the conductive plate <NUM>. The conductive plate <NUM> is constructed of a conductive material, such as copper, aluminum or the like. The dielectric material <NUM> is constructed of a non-conductive material, such as a ceramic material, a polymer material or the like.

The transducer array <NUM> also includes a plurality of isolated conductive gel elements <NUM>, one of which is shown by way of example in <FIG>. The isolated conductive gel element <NUM> is in contact with the electrode element <NUM>. The dielectric material <NUM> is positioned between the isolated conductive gel element <NUM>, and serves to capacitively couple the conductive plate <NUM>, and the isolated conductive gel element <NUM>. The isolated conductive gel element <NUM> includes the first conductive gel layer 106a and the second conductive gel layer 106b. The support layer <NUM> is optional, and when present may be positioned in between the first conductive gel layer 106a in the second conductive gel layer 106b. As shown in <FIG>, the first conductive gel layer 106a overlaps the second conductive gel layer 106b. As will be explained in more detail below, the first conductive gel layer 106a may be applied to the plurality of electrode elements <NUM> in a flowable state, and then cured on the electrode elements <NUM>. The first side 115a of the support layer <NUM> may be applied onto the first conductive gel layer 106a, and the second conductive gel layer 106b, in a flowable state, may be applied onto the second side 115b of the support layer <NUM> such that the first and second conductive gel layers 106a and 106b on each of the electrode elements <NUM> overlap. Once the second conductive gel layer 106b is applied, the second conductive gel layer 106b may be cured on the second side 115b of the support layer <NUM>. As discussed above, the support layer <NUM> may be provided with a plurality of pores which permit the second conductive gel layer 106b to flow through the pores and engage the first conductive gel layer 106a prior to curing the second conductive gel layer 106b.

The release liner <NUM> is in contact with and covers the second conductive gel layer 106b. The release liner <NUM> may be applied to the second conductive gel layer 106b subsequent to curing the second conductive gel layer 106b.

The first conductive gel layer 106a may have a thickness of within a range of approximately <NUM> to approximately <NUM> and combinations therein (e. g, a range of from <NUM> to about <NUM>, a range of from about. <NUM> to about <NUM>, etc.). The second conductive gel layer 106b may have a thickness within a range of approximately <NUM> to approximately <NUM> and combinations therein (e.g., a range of from <NUM> to about <NUM>, a range of from about. <NUM> to about <NUM>, etc.).

Any dielectric polymer material(s) known in the art or otherwise contemplated herein may be present in the electrodes utilized in accordance with the present disclosure. Non-limiting examples of polymers that may be utilized to form the electrode (and in particular, to form a polymer layer of an electrode) include PVDF, poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene), and/or poly(vinylidene f!uoride-trifiuoroethytene-<NUM>-chlorofluoroethylene). Those two polymers are abbreviated herein as "Poly(VDF-TrFE-CtFE)" and "Poly(VDF-TrFE-CFE)," respectively. These polymers have a high dielectric constant (i.e., on the order of <NUM>). Alternatively, other polymer(s) that provides a high level of capacitance (i.e., a dielectric constant of at least <NUM> at least one frequency between <NUM> and <NUM>) may be used.

In addition, in certain non-limiting embodiments, ceramic nanoparticles may be mixed into the polymer to form a "nanocomposite. " Optionally, these ceramic nanoparticles may comprise ferroelectric metal oxides (e.g., at least one of barium titanate and barium strontium titanate).

When the electrode element <NUM> comprises a conductive material layer and a flexible polymer layer, the layer of conductive material may comprise at least one metal (such as, but not limited to, stainless steel, gold, and/or copper).

When the dielectric material <NUM> is constructed of a ceramic material, the ceramic material may be porous. When the first conductive gel layer 106a is applied to the dielectric material <NUM>, a portion of the first conductive gel layer 106a in the flowable state may flow into the pores and thereby penetrate the dielectric material prior to curing the first conductive gel layer 106a. Once cured, the portions of the first conductive gel layer 106a penetrating the dielectric material <NUM> enhance the adhesion of the first conductive gel layer 106a to the dielectric material <NUM>.

When the dielectric material <NUM> is constructed of a non-ceramic material, such as a flexible or non-flexible polymer material, a surface of the polymer material may be treated to enhance adhesion between the first conductive gel layer 106a and the dielectric material <NUM>. The use of a polymer in the production of the electrode element <NUM> may provide crosslinking between the conductive gel element <NUM> and the polymer of the electrode element <NUM> during a curing step. Chemical bonding may provide a mechanical connection therebetween that cannot be achieved with electrodes formed of only ceramic materials. Such bonding may aid in maintaining of the conductive gel element <NUM> on the array for a longer period of time, improved adhesion rate for a longer period of time, improved contact with skin of a patient, reduction of replacement rate of arrays, and/or the like. Examples of manners to treat the polymer material will be described below.

As shown in <FIG>, the electrode element <NUM> is connected to and supported by the flex circuit <NUM>. As shown, the electrode element <NUM> extends over a portion of the flex circuit <NUM>. The flex circuit <NUM> is connected to the covering adhesive backed layer <NUM>.

Referring now to <FIG>, shown therein is the electrode element <NUM>. The electrode element <NUM> is provided with the conductive plate <NUM> and the dielectric material <NUM> as described above. In the example shown in <FIG>, the dielectric material <NUM> is constructed of a non-porous material, such as a polymer. To enhance adhesion with the conductive gel layer 106a, the dielectric material <NUM> is provided with a textured surface <NUM>. The textured surface <NUM> can be formed by any suitable process, such as abrasion, chemical etching, blasting, grinding, plasma treatment, ozone treatment, and/or the like. The textured surface <NUM> is spaced a distance away from the conductive plate <NUM>.

Referring now to <FIG>, shown therein is a partial schematic view of another embodiment of a transducer array 100a constructed in accordance with the present disclosure. The transducer array 100a is identical in construction and function as the transducer array <NUM> discussed above, except that the transducer array 100a is provided with the plurality of electrode elements 110a. <FIG> is a cross-sectional view taken across one of the electrode elements 110a. The electrode element 110a is provided with a conductive layer <NUM>, which is mechanically and electrically connected to the first conductive gel layer 106a.

Referring now to <FIG>, shown therein is the electrode element 110a. The electrode element 110a is provided with the conductive layer <NUM> as described above. To enhance adhesion with the conductive gel layer 106a, the conductive layer <NUM> is provided with a textured surface <NUM>. The textured surface <NUM> can be formed by any suitable process, such as abrasion, chemical etching, blasting, grinding, plasma treatment, ozone treatment, and/or the like.

Referring now to <FIG>, shown therein is a diagram of an exemplary embodiment of a gel application system <NUM> constructed in accordance with the present disclosure that applies the first conductive gel layer 106a and/or the second conductive gel layer 106b to the electrode element <NUM> or 110a. The gel application system <NUM> comprises one or more applicator <NUM> and a platform <NUM> moveably attached to a housing <NUM>. Only one applicator <NUM> is shown for purposes of brevity. It should be understood that multiple applicators <NUM> can also be used. The one or more applicator <NUM> further comprises at least a nozzle <NUM> to eject a conductive gel, described in more detail above. The platform <NUM> supports a plurality of electrode elements <NUM> or 110a of the transducer arrays <NUM> or 100a. The plurality of electrode elements <NUM> or 110a may be connected to and supported by the flex circuit <NUM> and/or the cover adhesive-backed layer <NUM> in the first predetermined pattern discussed above. The cover adhesive-backed layer <NUM> may engage and be supported by the platform <NUM>. In one embodiment, the applicator <NUM> may move in one of a first direction <NUM> or a second direction <NUM> or a combination of the first direction <NUM> and the second direction <NUM>. In one embodiment, the platform <NUM> may move in one of the first direction <NUM> or the second direction <NUM> or a combination of the first direction <NUM> and the second direction <NUM>. In one embodiment, the gel application system <NUM> includes a controller <NUM> to control movement of the platform <NUM> and/or to control movement of the applicator <NUM>.

In one embodiment, the nozzle <NUM> has an application distance determined by the distance between the nozzle <NUM> from the platform <NUM>, and ejects conductive gel (in liquid form) at an application pressure, and moves at an application velocity relative to the platform <NUM>. By adjusting the application distance, the application pressure, and the application velocity, the amount of conductive gel applied by the nozzle <NUM> can be adjusted. The application velocity may be caused by moving the applicator <NUM> and/or the platform <NUM> in one of the first direction <NUM>, the second direction <NUM>, or the combination of the first direction <NUM> and the second direction <NUM>.

In one embodiment, the application pressure is selected such that a portion of the conductive gel is wicked into pores of the dielectric material <NUM> when the dielectric material <NUM> is porous, or wicked into the valleys <NUM> or <NUM> so that a contact area, that is an area of the electrode element <NUM> or 110a and the first conductive gel layer 106a in contact, is increased. For example, it may be desirable to eject conductive gel at a higher pressure to cause the conductive gel to penetrate further into the ceramic material. By increasing penetration into the ceramic material, adhesion between the electrode element <NUM> and the first conductive gel layer 106a may be increased.

In one embodiment, the gel application system <NUM> ejects conductive gel in a liquid form (e.g., a flowable state) onto the textured surface <NUM> or <NUM>. Once the gel application system <NUM> ejects conductive gel onto a particular electrode element <NUM> or 110a, the gel application system <NUM> may eject conductive gel onto another one or more of the electrode elements <NUM> or 110a until the conductive gel has been applied to all of the electrode elements <NUM> or 110a. Once the conductive gel is applied, the conductive gel is cured on the electrode elements <NUM> or 110a. For example, the liquid conductive gel may be exposed to a UV light emitted by a UV source to cure the liquid conductive gel into a non-flowable state, e.g., polymerized. The polymerized conductive gel may form the first conductive gel layer 106a.

In one embodiment, the applicator <NUM> may be hand-held, that is, the applicator <NUM> may be held and/or moved by a user instead of being moveably attached to the housing <NUM>. In such an embodiment, the user may use the applicator <NUM> to ejectconductivegel onto the dielectric material <NUM> of the conductive layer <NUM>.

Once the first conductive gel layer 106a is formed, the support layer <NUM> may be applied to the electrode elements <NUM> or 110a, and then the applicator <NUM> may be used to apply conductive gel onto the support layer <NUM> to form the second conductive gel layer 106b. As discussed above, the support layer <NUM> is optional and therefore applying the support layer <NUM> to the first conductive gel layer 106a is also optional.

Shown in <FIG> is a process <NUM> for making at least one tumor treating field electrode <NUM> (see <FIG>). The tumor treating field electrode <NUM> is a conductive gel assembly. More particularly, at a step <NUM>, a conductive gel is dispensed, in a flowable state, on one of the electrode elements <NUM> or 110a of the transducer array <NUM> or 100a operable for the delivery of tumor treating fields. Then, at a step <NUM>, the conductive gel is cured on the electrode element <NUM> or 110a such that the conductive gel is in a non-flowable state.

Shown in <FIG> is a process <NUM> for making the transducer array <NUM> or 100a. In a step <NUM>, an electrode layer having a plurality of electrode elements <NUM> or 110a configured to receive an electrical signal from an electric field generator producing an electric signal as a TTField is provided. The electrode elements <NUM> or 110a are electrically isolated. In a step <NUM>, conductive gel elements <NUM> are applied in a flowable state to the plurality of electrode elements <NUM> or 110a. In a step <NUM>, the conductive gel elements are cured on the electrode elements.

Claim 1:
A method, comprising:
dispensing a first conductive gel on a first side (115a) of a support layer (<NUM>) in a first predetermined pattern of target locations to form a plurality of first conductive gel layers (106a), the support layer (<NUM>) being a flexible material having a plurality of voids intersecting the first side (115a) and a second side (115b) of the support layer (<NUM>);
dispensing a second conductive gel on the second side (115b) of the support layer (<NUM>) in a second predetermined pattern of target locations to form a plurality of second conductive gel layers (106b), with each of the second conductive gel layers (106b) overlapping a corresponding first conductive gel layer (106a) to form conductive gel elements (<NUM>); and
curing the first conductive gel and the second conductive gel.