Flexible Electrode Arrays

An apparatus has an electrode subassembly having a circuitry layer having a skin-facing inner side and an outer side. A plurality of electrode elements are disposed on the inner side of the circuitry layer and electrically coupled to the circuitry layer. Each electrode element of the plurality of electrode elements has an electrode edge. A layer of anisotropic material is electrically coupled to the plurality of electrode elements of the electrode subassembly. The layer of anisotropic material has a skin-facing surface and an opposing outwardly facing surface. The layer of anisotropic material has a peripheral outer edge. The peripheral outer edge of the layer of anisotropic material extends beyond the electrode edge of each respective electrode element of the plurality of electrode elements. A skin contact layer comprises a biocompatible conductive material. The skin contact layer is disposed on a skin-facing side of the layer of anisotropic material.

BACKGROUND

Tumor Treating Fields (TTFields) therapy is a proven approach for treating tumors using alternating electric fields at frequencies between 50 kHz-1 MHz, more commonly, 100-500 kHz. In current commercial systems, the alternating electric fields are induced by electrode assemblies (e.g., arrays of capacitively coupled electrodes, also called transducer arrays) placed on opposite sides of a target region of the subject's body. When an AC voltage is applied between opposing electrode assemblies, an AC current is coupled through the electrode assemblies and into the subject's body. And higher currents are strongly correlated with higher efficacy of treatment.

SUMMARY

TTFields are approved for the treatment of glioblastoma multiforme (GBM), and may be delivered, for example, via the OPTUNE® system (Novocure Limited, St. Helier, Jersey), which includes transducer arrays placed on the patient's shaved head. More recently, TTFields therapy has been approved as a combination therapy with chemotherapy for malignant pleural mesothelioma (MPM), and may find use in treating tumors in other parts of the body. For applications targeting tumors in the torso, larger electrode arrays than currently used with the OPTUNE® system may be beneficial. What is needed is a larger area electrode array that is flexible enough to move with the body and be worn comfortably, while minimizing exposed printed circuit board (PCB) edges which can cause discomfort. Disclosed herein are flexible electrode arrays with minimal exposed PCB edges, which can be scaled to any area size including large areas suitable for torso applications.

Disclosed herein, in one aspect, an apparatus having an electrode subassembly having a circuitry layer and a plurality of electrode elements. The circuitry layer has a skin-facing inner side and an outer side. The plurality of electrode elements are disposed on the inner side of the circuitry layer and electrically coupled to the circuitry layer. Each electrode element of the plurality of electrode elements has an electrode edge. A layer of anisotropic material is electrically coupled to the plurality of electrode elements of the electrode subassembly. The layer of anisotropic material is disposed on an inner side of each of the plurality of electrode elements and has a skin-facing surface and an opposing outwardly facing surface. The layer of anisotropic material has a peripheral outer edge. The peripheral outer edge of the layer of anisotropic material extends beyond the electrode edge of each respective electrode element of the plurality of electrode elements. A skin contact layer comprises a biocompatible conductive material. The skin contact layer is disposed on a skin-facing side of the layer of anisotropic material.

In one aspect, an apparatus comprises an electrode subassembly having a circuitry layer and a plurality of electrode elements. The circuitry layer has a skin-facing inner side and an outer side and comprises a primary branch that extends along a first axis. The plurality of electrode elements are disposed on the inner side of the circuitry layer and electrically coupled to the circuitry layer. Each electrode element of the plurality of electrode elements has an electrode edge. A layer of anisotropic material is electrically coupled to the plurality of electrode elements of the electrode subassembly, the layer of anisotropic material having a skin-facing surface and an opposing outwardly facing surface. The layer of anisotropic material has a peripheral outer edge, wherein the peripheral outer edge of the layer of anisotropic material extends beyond the electrode edge of each respective electrode element of the plurality of electrode elements. A skin contact layer comprises a biocompatible conductive material. The skin contact layer is disposed on a skin-facing side of the layer of anisotropic material. The plurality of electrode elements include first and second electrode elements positioned on a first side of the primary branch and third and fourth electrode elements positioned on a second side of the primary branch. The second side is spaced from the first side along or parallel to a second axis that is perpendicular to the first axis. At least one of the first and second electrode elements positioned on the first side of the primary branch and at least one of the third and fourth electrode elements positioned on the second side of the primary branch are mechanically coupled to the primary branch in a manner that provides mechanical support and flexibility along both the first axis and the second axis.

Methods of using the apparatuses are also disclosed.

Various embodiments are described in detail below with reference to the accompanying drawings, wherein like reference numerals represent like elements, and wherein descriptions of like elements may not be repeated for every embodiment, but may be considered to be the same if previously described herein.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

This application describes exemplary electrode assemblies that may be used, e.g., for delivering TTFields to a subject's body and treating one or more cancers or tumors located in the subject's body.

The present invention can be understood more readily by reference to the following detailed description, examples, drawings, and claims, and their previous and following description. However, it is to be understood that this invention is not limited to the specific apparatuses, devices, systems, and/or methods disclosed unless otherwise specified, and as such, of course, can vary.

Headings are provided for convenience only and are not to be construed to limit the invention in any manner. Embodiments illustrated under any heading or in any portion of the disclosure may be combined with embodiments illustrated under the same or any other heading or other portion of the disclosure.

Any combination of the elements described herein in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, disclosure of “a layer” can represent disclosure of embodiments in which only a single layer is provided, as well as disclosure of embodiments in which a plurality of such layers are provided.

In the preceding and following description, the terms “front,” “inner,” and “skin-facing” are used interchangeably to refer to a face or surface of the disclosed electrode assemblies (or components thereof) that faces or is oriented toward the skin of a subject (or generally toward the body of a subject) when used as disclosed herein. Similarly, the terms “rear,” “upper,” “outer,” and “outwardly facing” are used interchangeably to refer to a face or surface of the disclosed electrode assemblies (or components thereof) that faces away from or is oriented away from the skin of a subject (or generally away from the body of the subject) when used as disclosed herein.

Structure and Configuration of Apparatus

Referring toFIGS.1and2, an apparatus10can comprise an electrode subassembly20having a circuitry layer22and a plurality of electrode elements30(e.g., electrode elements30a-dinFIG.1). The circuitry layer22has a skin-facing inner side24and an outer side26. The plurality of electrode elements30can be disposed on the inner side24of the circuitry layer22and can be electrically coupled to the circuitry layer22. Each electrode element30of the plurality of electrode elements can have an electrode edge32. The circuitry layer22can optionally comprise (or be) a printed circuit board (PCB).

A layer of anisotropic material40can be electrically coupled to the plurality of electrode elements30of the electrode subassembly20. The layer of anisotropic material40can have a skin-facing surface42and an opposing outwardly facing surface44. The layer of anisotropic material40can have a peripheral outer edge46. The peripheral outer edge46of the layer of anisotropic material40can extend beyond the electrode edge32of each respective electrode element30of the plurality of electrode elements. In an embodiment, the peripheral outer edge46of the layer of anisotropic material40can extend beyond the electrode edge32of each respective electrode element30of the plurality of electrode elements by at least 1 mm, or at least: 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 15 mm, 20 mm, 30 mm, 40 mm, or 50 mm.

The apparatus10can further comprise a skin contact layer60comprising a biocompatible conductive material. The skin contact layer60can be disposed on a skin-facing side48of the layer of anisotropic material40, and, when the apparatus is in use treating a patient, the skin contact layer60can be in contact with the subject's skin200. Optionally, the skin contact layer60can be disposed against the skin-facing surface42of the layer of anisotropic material40. In some aspects, the skin contact layer60can be or comprise hydrogel. In other aspects, the skin contact layer60can be or comprise a conductive adhesive composite.

In some aspects, the circuitry layer22can comprise a primary branch70that extends along a first axis72. The plurality of electrode elements30can comprise at least one electrode element (e.g., electrode elements30a,b) positioned on a first side74of the primary branch70and at least one electrode element (e.g., electrode element30c,d) positioned on a second side76of the primary branch. The second side76can be spaced from the first side74along or parallel to a second axis78that is perpendicular to the first axis72.

In various aspects, at least one electrode element30positioned on the first side74of the primary branch70(e.g., first and/or second electrode elements30a,b) and at least one electrode element30positioned on the second side76of the primary branch70(e.g., third and/or fourth electrode elements30c,d) can be mechanically coupled to the primary branch in a manner that provides mechanical support and flexibility along both the first axis72and the second axis78.

In some aspects, the one or more of the electrode elements30positioned on the first side74of the primary branch70can comprise first and second electrode elements30a,bpositioned on the first side of the primary branch. In further aspects, the one or more of the electrode elements30positioned on the second side76of the primary branch70can comprise third and fourth electrode elements30c,dpositioned on the second side76of the primary branch70.

The circuitry layer22can comprise a first secondary branch80athat extends away from a first end portion82of the primary branch70in a first direction along or parallel to the second axis78. A second secondary branch80bcan extend away from the first end portion82of the primary branch70in a second direction along or parallel to the second axis78that is opposite the first direction. The first secondary branch80acan electrically and mechanically couple the first electrode element30ato the primary branch70. The second secondary branch80bcan electrically and mechanically couple the third electrode element30cto the primary branch70.

The circuitry layer22can further comprise a first tertiary branch86athat extends away from the first electrode element30aalong or parallel to the first axis72in a direction toward a second end portion84of the primary branch70and a second tertiary branch86bthat extends away from the third electrode element30calong or parallel to the first axis72in the direction toward the second end portion84of the primary branch70. The first tertiary branch86acan electrically and mechanically couple the second electrode element30bto the first secondary branch80a, and the second tertiary branch86bcan electrically and mechanically couple the fourth electrode element30dto the second secondary branch80b.

The respective electrode edges32of the second and fourth electrode elements30b,dcan be spaced from the primary branch70along or parallel to the second axis78.

In some optional aspects, each electrode element30of the plurality of electrode elements can comprise a first end edge32athat is parallel or substantially parallel to the first axis72. The first end edge32aof each electrode element30can face the primary branch70.

In further optional aspects, each electrode element30of the plurality of electrode elements can further comprise an opposing second end edge32bthat is rounded and that faces a periphery46of the layer of anisotropic material40.

Each electrode element30of the plurality of electrode elements can further comprise first and second side edges32c,dthat extend between the first and second end edges32a,bof the electrode element.

In some optional aspects, and with reference toFIG.3, each electrode element30of the plurality of electrode elements can comprise a second end edge32bthat is parallel or substantially parallel to the first axis72and that faces a periphery46of the layer of anisotropic material40.

In some aspects, at least one electrode element30of the plurality of electrode elements can have a circular or oval shape. That is, the electrode edge32of at least one electrode element can be circular or oval.

The primary branch70of the circuitry layer22can have a length. In some optional aspects, the primary branch70of the circuitry layer22(e.g., the PCB) can be wrapped in a polymeric protective covering along a portion of, most of, substantially all of, or all of, the length of the primary branch. The polymeric protective covering can cover the edges of the primary branch70(e.g., PCB edges). In this way, the polymeric protective coating can minimize any discomfort from the PCB edges contacting the subject's skin200. Further optionally, fewer electrode elements30translates to fewer areas of exposed PCB connecting the electrode elements30(and fewer exposed PCB edges). For example,FIG.1andFIG.3illustrate electrode arrays having just4electrode elements30, thereby minimizing the number of PCB edges, while allowing flexibility in directions moving around, for example, a first axis72and a second axis78.

In some optional aspects, the apparatus10can comprise a conductive layer50positioned between a respective skin-facing surface34of each of the plurality of electrode elements30and the outwardly facing surface44of the layer of anisotropic material40. In further optional aspects, the conductive layer50can be, or comprise, a layer of hydrogel. In further optional aspects, the conductive layer50can be, or comprise, a layer of conductive adhesive composite. The conductive layer50(e.g., layer of hydrogel or layer of conductive adhesive composite) can be configured to facilitate electrical contact between the plurality of electrode elements30and the outwardly facing surface44of the layer of anisotropic material40. In some optional aspects, the conductive layer50can be omitted from the apparatus10.

Optionally, the apparatus10can comprise a covering layer90having an inner side92and an outer side94. The inner side92can be disposed on the outer side of the circuitry layer22. Portions of the covering layer90can extend beyond the electrode edge32of each of the electrode elements30and beyond a periphery of (e.g., the peripheral outer edge46of) the layer of anisotropic material40to define at least one attachment surface96.

The apparatus10can further comprise a single wire100(FIG.1) that is configured to electrically couple the electrode subassembly to a current source (e.g., an AC voltage generator820(FIG.4)).

The electrode subassembly20can have a total areal footprint, and the layer of anisotropic material40can have a total areal footprint. In some optional aspects, a ratio of the total areal footprint of the electrode subassembly20to the total areal footprint of the layer of anisotropic material 40 can be from 20% to 95%, such as, for example, 25% to 90%, or 25% to 85%; and can range from as low as 20%, or 25%, or 30%, or 40%, or 50%, or 60%, or 70%, and up to as high as 50%, or 60%, or 70%, or 80%, or 85%, or 90%, or 95%, in any combination of endpoints in the range.

In some optional aspects, each electrode element30can comprise a metallic layer110having a skin-facing surface112and a layer of dielectric material120. The layer of dielectric material120can be disposed on the skin-facing side of the metallic layer110, such as on the skin-facing surface112of the metallic layer110, and can be electrically coupled to the outwardly facing surface44of the layer of anisotropic material40. In some aspects, the dielectric material120can comprise ceramic material. In other aspects, the dielectric material120can comprise polymer film. In exemplary aspects, the dielectric material120can have a dielectric constant ranging from10to50,000. In some embodiments, the layer of dielectric material120comprises a high dielectric polymer material such as poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) and/or poly(vinylidene fluoride-trifluoroethylene-1-chlorofluoroethylene). Those two polymers are abbreviated herein as “Poly(VDF-TrFE-CTFE)” and “Poly(VDF-TrFE-CFE),” respectively. These embodiments are particularly advantageous because the dielectric constant of these materials is on the order of 40. In some embodiments, the polymer layer can be poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene-chlorofluoroethylene) or “Poly(VDF-TrFE-CTFE-CFE).” In some embodiments, the layer of dielectric material70comprises a terpolymer comprising polymerized units of monomers such as VDF, TrFE, CFE and/or CTFE in any suitable molar ratio. Suitable terpolymers include those, for example, having 30 to 80 mol % VDF, 5 to 60 mol % TrFE, with CFE and/or CTFE constituting the balance of the mol % of the terpolymer.

In alternative aspects, the electrode elements30do not comprise a dielectric material.

In some optional aspects, the anisotropic material40can comprise graphite. In some optional aspects, the graphite can comprise synthetic graphite. The layer of anisotropic material can be, or can comprise, a layer of pyrolytic graphite, graphitized polymer film, or graphite foil made from compressed high purity exfoliated mineral graphite. Examples of suitable forms of graphite include synthetic graphite, such as pyrolytic graphite (including, but not limited to, Pyrolytic Graphite Sheet (PGS), available from Panasonic Industry, Kadoma, Osaka, Japan), other forms of synthetic graphite, including but not limited to, graphite foil made from compressed high purity exfoliated mineral graphite (including, but not limited to, that supplied by MinGraph® 2010A Flexible Graphite, available from Mineral Seal Corp., Tucson, Arizona, USA), or graphitized polymer film, e.g., graphitized polyimide film, (including, but not limited to, that supplied by Kaneka Corp., Moka, Tochigi, Japan. In alternative embodiments, conductive anisotropic materials other than graphite may be used instead of graphite.

In some aspects, the layer of anisotropic material40has a first thermal conductivity in a direction that is perpendicular to a plane of the layer. The thermal conductivity of the layer of anisotropic material40in directions that are parallel to the plane of the layer of anisotropic material can be more than two times higher than the first thermal conductivity. For example, in some aspects, the thermal conductivity of the layer of anisotropic material40in directions that are parallel to the plane of the layer of anisotropic material can be more than three times higher, more than four times higher, or more five than the first thermal conductivity. In some aspects, the thermal conductivity in the parallel directions is more than ten times higher than the first thermal conductivity. In various aspects, the thermal conductivity of the layer of isotropic material40in directions that are parallel to the plane of the layer of anisotropic material can be more than: 1.5 times, 2 times, 3 times, 5 times, 10 times, 20 times, 100 times, 200 times, or even more than 1,000 times higher than the first thermal conductivity. The use of a layer of anisotropic material40in the electrode array facilitates the current entering the body over a larger area, and may be advantageous in larger arrays, such as those intended for use on the torso.

The layer of anisotropic material40can have a first resistance in a direction that is perpendicular to a plane of the layer. In some optional aspects, resistance of the layer in directions that are parallel to the plane of the layer is less than half the first resistance. In exemplary aspects, the resistance of the layer of anisotropic material40in directions that are parallel to the plane of the layer can be less than 10% of the first resistance. In exemplary aspects, the resistance of the layer of anisotropic material40in directions that are parallel to the plane of the layer can be less than 75%, 50%, 40%, 30%, 20%, 10%, 5%, 1%, 0.5%, or even less than 0.1% of the first resistance.

In some optional aspects, the layer of anisotropic material40can be omitted from the apparatus10.

In some aspects, the skin contact layer60may be a layer of hydrogel. In some aspects, the skin contact layer60may be a layer of conductive adhesive composite. In some aspects, the conductive layer50may be a layer of hydrogel. In some aspects, the conductive layer50may be a layer of conductive adhesive composite.

In exemplary aspects, the conductive adhesive composite of any of the layers of the apparatus10(e.g., the skin contact layer60and/or the conductive layer50) can comprise a dielectric material and conductive particles dispersed within the dielectric material. In some embodiments, at least a portion of the conductive particles define a conductive pathway through a thickness of the conductive adhesive composite. It is contemplated that the conductive particles can be aligned in response to application of an electric field such that the conductive particles undergo electrophoresis. In some aspects, the dielectric material of the conductive adhesive composite can be a polymeric adhesive. Optionally, in these aspects, the polymeric adhesive can be an acrylic adhesive or a silicone adhesive. In some aspects, the conductive particles can comprise carbon. Optionally, in these aspects, the conductive particles can comprise graphite powder. Additionally, or alternatively, the conductive particles can comprise carbon flakes. Additionally, or alternatively, the conductive particles can comprise carbon granules. Additionally, or alternatively, the conductive particles can comprise carbon fibers. Additionally, or alternatively, the conductive particles can comprise carbon nanotubes or carbon nanowires. Additionally, or alternatively, the conductive particles can comprise carbon black powder. In further aspects, the conductive adhesive composite further comprises a polar material (e.g., a polar salt). The polar salt may be a quaternary ammonium salt, such as a tetra alkyl ammonium salt. Exemplary conductive adhesive composites, as well as methods for making such conductive adhesive composites, are disclosed in U.S. Pat. No. 8,673,184 and U.S. Pat. No. 9,947,432, which are incorporated herein by reference for all purposes. In exemplary aspects, the conductive adhesive composite can be a dry carbon/salt adhesive.

In exemplary aspects, the conductive layer50or the skin contact layer60can comprise a conductive adhesive composite provided by ADHESIVE RESEARCH, such as ARcare® 8006 electrically conductive adhesive composition manufactured and sold by Adhesives Research, Inc. (Glen Rock, PA, USA). In other optional aspects, the conductive layer50and/or the skin contact layer60can comprise carbon fibers or nanowires. For example, in exemplary aspects, the conductive layer50and/or the skin contact layer60can comprise a dry carbon/salt adhesive, such as the developmental product FLX068983—FLEXcon® OMNI-WAVE™ TT 200 BLACK H-502 150 POLY H-9 44PP-8 from FLEXcon, Spencer, MA, USA, or other such OMNI-WAVE products from FLEXcon.

In various aspects, the conductive layer50can have a thickness from about 25 μm to about 150 μm. In various aspects, the skin contact layer60can have a thickness from about 25 μm to about 150 μm.

EXEMPLARY METHOD OF USE OF APPARATUS

Referring toFIG.4, a method can comprise applying an electrical field using at least one electrode subassembly20of the apparatus10, where components of apparatus10can be as described above (and as labelled inFIGS.1-3). For example, at least first and second apparatuses10a,bcan be positioned on a body of a subject or within the body of a subject. The skin contact layer60of each of the first and second apparatuses10a,bcan contact skin200(FIG.2) of the subject. An alternating voltage can be applied between the first apparatus10aand the second apparatus10b, thereby generating an electric field.

The alternating voltage between the first apparatus10aand the second apparatus10bcan be applied by an AC voltage generator820. In some embodiments, the frequency of the alternating voltage is between 50 kHz and 1 MHz, or between 100 kHz and 500 kHz. In the illustrated example, the AC voltage generator is controlled by a controller822. The controller822may use temperature measurements to control the amplitude of the current to be delivered via the first and second apparatus10a,bin order to maintain temperatures below a safety threshold (e.g., 41° C.). This may be accomplished, for example, by measuring a first temperature of a first electrode element30, measuring a second temperature of a second electrode element30, and controlling the applying of the alternating voltage based on the first temperature and the second temperature, as described below.

FIG.4depicts one example of hardware that is suitable for this purpose. More specifically, temperature sensors800(e.g., thermistors) are positioned in thermal contact with respective electrode elements30(for example, dielectric material120/layer of metal110) within each of the apparatuses10a,b. The temperature sensors800measure respective first and second temperatures (e.g., at first and second electrode elements in the first electrode assembly and second electrode assembly, respectively), and the controller822controls the output of the AC voltage generator820based on these temperatures.

Optionally, prior to applying the electrical field, a shape and/or size of the apparatus10can be adjusted by cutting through a peripheral portion of the layer of anisotropic material40that is positioned beyond the electrode edge32of each respective electrode element30of the plurality of electrode elements.

EXEMPLARY EMBODIMENTS

Referring toFIGS.1-2, an apparatus10can comprise an electrode subassembly20having a circuitry layer22, the circuitry layer having a skin-facing inner side24and an outer side26. The circuitry layer22can comprise a primary branch70that extends along a first axis72. A plurality of electrode elements30can be disposed on the inner side24of the circuitry layer22and can be electrically coupled to the circuitry layer22. Each electrode element30of the plurality of electrode elements can have an electrode edge32.

A layer of anisotropic material40can be electrically coupled to the plurality of electrode elements30of the electrode subassembly20. The layer of anisotropic material40can have a skin-facing surface42and an opposing outwardly facing surface44. The layer of anisotropic material40can have a peripheral outer edge46. In some optional aspects, the peripheral outer edge46of the layer of anisotropic material40can extend beyond the electrode edge32of each respective electrode element30of the plurality of electrode elements. In some optional aspects, the peripheral outer edge46of the layer of anisotropic material40can extend beyond the electrode edge32of each respective electrode element30of the plurality of electrode elements by at least 1 mm, or at least: 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 15 mm, 20 mm, 30 mm, 40 mm, or 50 mm.

The apparatus10can further comprise a skin contact layer60comprising a biocompatible conductive material. The skin contact layer60can be disposed on a skin-facing side48of the layer of anisotropic material40. Optionally, the skin contact layer60can be disposed against the skin-facing surface42of the layer of anisotropic material40. In some aspects, the skin contact layer can be hydrogel. In other aspects, the skin contact layer can be a conductive adhesive composite.

In some optional aspects, the apparatus10can further comprise the same components as described earlier for apparatus10. For example, the apparatus10can comprise a conductive layer50positioned between a respective skin-facing surface34of each of the plurality of electrode elements30and the outwardly facing surface44of the layer of anisotropic material40. In further optional aspects, the conductive layer50can be, or comprise, a layer of hydrogel. In further optional aspects, the conductive layer50can be, or comprise, a layer of conductive adhesive composite.

The plurality of electrode elements comprise first and second electrode elements30a,bpositioned on a first side74of the primary branch70and third and fourth electrode elements30c,dpositioned on a second side76of the primary branch70. The second side76can be spaced from the first side74along or parallel to a second axis78that is perpendicular to the first axis72.

In various aspects, at least one of the first and second electrode elements30a,bpositioned on the first side74of the primary branch70and at least one of the third and fourth electrode elements30c,dpositioned on the second side76of the primary branch70can be mechanically coupled to the primary branch in a manner that provides mechanical support and flexibility along both the first axis72and the second axis78.

The electrode subassembly20can have a total areal footprint, and the layer of anisotropic material40can have a total areal footprint. In some optional aspects, a ratio of the total areal footprint of the electrode subassembly20to the total areal footprint of the layer of anisotropic material40can be from 20% to 95%, such as, for example, 25% to 90%, or 25% to 85%; and can range from as low as 20%, or 25%, or 30%, or 40%, or 50%, or 60%, or 70%, and up to as high as 50%, or 60%, or 70%, or 80%, or 85%, or 90%, or 95%, in any combination of endpoints in the range.

The exemplary embodiments can be used in accordance with methods disclosed herein.

EXEMPLARY ASPECTS

In view of the described products, systems, and methods and variations thereof, herein below are described certain more particularly described aspects of the invention. These particularly recited aspects should not however be interpreted to have any limiting effect on any different claims containing different or more general teachings described herein, or that the “particular” aspects are somehow limited in some way other than the inherent meanings of the language literally used therein.

Aspect 1. An apparatus comprising:an electrode subassembly having:a circuitry layer having a skin-facing inner side and an outer side; anda plurality of electrode elements disposed on the inner side of the circuitry layer and electrically coupled to the circuitry layer, wherein each electrode element of the plurality of electrode elements has an electrode edge and an inner side;a layer of anisotropic material electrically coupled to the plurality of electrode elements of the electrode subassembly, the layer of anisotropic material disposed on the inner side of each electrode element of the plurality of electrode elements and having a skin-facing surface and an opposing outwardly facing surface, the layer of anisotropic material having a peripheral outer edge, wherein the peripheral outer edge of the layer of anisotropic material extends beyond the electrode edge of each respective electrode element of the plurality of electrode elements; anda skin contact layer comprising a biocompatible conductive material, wherein the skin contact layer is disposed on a skin-facing side of the layer of anisotropic material.

Aspect 2. The apparatus of aspect 1, wherein the circuitry layer comprises a primary branch that extends along a first axis, wherein the plurality of electrode elements comprise:at least one electrode element positioned on a first side of the primary branch; andat least one electrode element positioned on a second side of the primary branch, wherein the second side is spaced from the first side along a second axis that is perpendicular to the first axis,wherein at least one of the at least one electrode element positioned on the first side of the primary branch and at least one of the at least one electrode element positioned on the second side of the primary branch are mechanically coupled to the primary branch in a manner that provides mechanical support and flexibility along both the first axis and the second axis.

Aspect 3. The apparatus of aspect 2, wherein the at least one electrode element positioned on the first side of the primary branch comprises first and second electrode elements positioned on the first side of the primary branch, and wherein the at least one electrode element positioned on the second side of the primary branch comprises third and fourth electrode elements positioned on the second side of the primary branch.

Aspect 4. The apparatus of aspect 3, wherein the circuitry layer comprises:a first secondary branch that extends away from a first end portion of the primary branch in a first direction along or parallel to the second axis; anda second secondary branch that extends away from the first end portion of the primary branch in a second direction along or parallel to the second axis that is opposite the first direction,wherein the first secondary branch electrically and mechanically couples the first electrode element to the primary branch, and wherein the second secondary branch electrically and mechanically couples the third electrode element to the primary branch.

Aspect 5. The apparatus of aspect 4, wherein the circuitry layer further comprises:a first tertiary branch that extends away from the first electrode element along or parallel to the first axis in a direction toward a second end portion of the primary branch; anda second tertiary branch that extends away from the third electrode element along or parallel to the first axis in the direction toward the second end portion of the primary branch,wherein the first tertiary branch electrically and mechanically couples the second electrode element to the first secondary branch, and wherein the second tertiary branch electrically and mechanically couples the fourth electrode element to the second secondary branch.

Aspect 6. The apparatus of aspect 5, wherein the respective electrode edges of the second and fourth electrode elements are spaced from the primary branch along or parallel to the second axis.

Aspect 7. The apparatus of any one of aspects 2-6, wherein each electrode element of the plurality of electrode elements comprises a first end edge that is parallel or substantially parallel to the first axis and that faces the primary branch.

Aspect 8. The apparatus of aspect 7, wherein each electrode element of the plurality of electrode elements further comprises an opposing second end edge that is rounded and that faces the peripheral outer edge of the layer of anisotropic material.

Aspect 9. The apparatus of aspect 8, wherein each electrode element of the plurality of electrode elements further comprises first and second side edges that extend between the first and second end edges of the electrode element.

Aspect 10. The apparatus of aspect 7, wherein each electrode element of the plurality of electrode elements further comprises an opposing second end edge that is parallel or substantially parallel to the first axis and that faces the peripheral outer edge of the layer of anisotropic material.

Aspect 11. The apparatus of any one of aspects 2-6, wherein at least one electrode element of the plurality of electrode elements has a circular or oval shape.

Aspect 12. The apparatus of any one of the preceding aspects, further comprising a layer of conductive adhesive composite positioned between a skin-facing surface of the plurality of electrode elements of the electrode subassembly and the outwardly facing surface of the layer of anisotropic material, wherein the layer of conductive adhesive composite is configured to facilitate electrical contact between the plurality of electrode elements and the outwardly facing surface of the layer of anisotropic material.

Aspect 13. The apparatus of any one of the preceding aspects, further comprising a covering layer having an inner side and an outer side, wherein the inner side is disposed on the outer side of the circuitry layer, wherein portions of the covering layer extend beyond the electrode edge of each of the electrode elements and beyond the peripheral outer edge of the layer of anisotropic material to define at least one attachment surface.

Aspect 14. The apparatus of any one of the preceding aspects, further comprising a single wire that is configured to electrically couple the electrode subassembly to a current source.

Aspect 15. The apparatus of any one of the preceding aspects, wherein the electrode subassembly has a total areal footprint, wherein the layer of anisotropic material has a total areal footprint, and wherein a ratio of the total areal footprint of the electrode subassembly to the total areal footprint of the layer of anisotropic material is from 20% to 95%.

Aspect 16. The apparatus of any one of the preceding aspects, wherein each electrode element comprises:a metallic layer having a skin-facing side and a skin-facing surface; anda layer of dielectric material, wherein the layer of dielectric material is disposed on the skin-facing side of the metallic layer and is electrically coupled to both of the metallic layer and the outwardly facing surface of the layer of anisotropic material.

Aspect 17. The apparatus of aspect 16, wherein the layer of dielectric material comprises a ceramic material.

Aspect 18. The apparatus of aspect 16, wherein the layer of dielectric material is a polymer film.

Aspect 19. The apparatus of any one of the preceding aspects, wherein the anisotropic material comprises graphite.

Aspect 20. The apparatus of any one of the preceding aspects, wherein the skin-contact layer is a hydrogel.

Aspect 21. The apparatus of any one of the preceding aspects, wherein the skin-contact layer is a conductive adhesive composite.

Aspect 22. The apparatus of any one of the preceding aspects, wherein the skin-contact layer is disposed on the skin-facing surface of the layer of anisotropic material.

Aspect 23. The apparatus of any one of the preceding aspects, wherein the anisotropic material comprises graphite, and wherein the peripheral outer edge of the layer of anisotropic material extends beyond the electrode edge of each respective electrode element of the plurality of electrode elements by at least 1 mm.

Aspect 24. A method comprising:applying an electrical field using the at least one electrode subassembly of the apparatus of any one of the preceding aspects.

Aspect 25. The method of aspect 24, further comprising, prior to applying the electrical field, adjusting a shape and/or size of the apparatus by cutting through a peripheral portion of the layer of anisotropic material that is positioned beyond the electrode edge of each respective electrode element of the plurality of electrode elements.

Aspect 26. An apparatus comprising:an electrode subassembly having:a circuitry layer having a skin-facing inner side and an outer side, wherein the circuitry layer comprises a primary branch that extends along a first axis; anda plurality of electrode elements disposed on the inner side of the circuitry layer and electrically coupled to the circuitry layer, wherein each electrode element of the plurality of electrode elements has an electrode edge;a layer of anisotropic material electrically coupled to the plurality of electrode elements of the electrode subassembly, the layer of anisotropic material having a skin-facing surface and an opposing outwardly facing surface, the layer of anisotropic material having a peripheral outer edge, wherein the peripheral outer edge of the layer of anisotropic material extends beyond the electrode edge of each respective electrode element of the plurality of electrode elements; anda skin contact layer comprising a biocompatible conductive material, wherein the skin contact layer is disposed on a skin-facing side of the layer of anisotropic material,wherein the plurality of electrode elements comprise:first and second electrode elements positioned on a first side of the primary branch; andthird and fourth electrode elements positioned on a second side of the primary branch, wherein the second side is spaced from the first side along or parallel to a second axis that is perpendicular to the first axis,wherein at least one of the first and second electrode elements positioned on the first side of the primary branch and at least one of the third and fourth electrode elements positioned on the second side of the primary branch are mechanically coupled to the primary branch in a manner that provides mechanical support and flexibility along both the first axis and the second axis.

Aspect 27. The apparatus of aspect 26, wherein the peripheral outer edge of the layer of anisotropic material extends beyond the electrode edge of each respective electrode element of the plurality of electrode elements by at least 1 mm.

Aspect 28. The apparatus of aspect 26 or aspect 27, wherein the electrode subassembly has a total areal footprint, wherein the layer of anisotropic material has a total areal footprint, and wherein a ratio of the total areal footprint of the electrode subassembly to the total areal footprint of the layer of anisotropic material is from 20% to 95%.

Aspect 29. A method comprising:applying an electrical field using the electrode subassembly of the apparatus of any one of aspects 26-28.