Electrode assembly having a non-hydrogel conductive adhesive layer and method of applying same to a tumor treatment field - Patents.com

Abstract

An electrode assembly having at least two layers of conductive adhesive material separated by an anisotropic material and a method of using the electrode assembly in a tumor treating field (TT field) treatment is disclosed.

Description

[Technical field]

[0001] [CROSS REFERENCE TO RELATED APPLICATIONS] This application claims priority to U.S. Provisional Application No. 63 / 280,440, filed November 17, 2021, which is incorporated by reference in its entirety. [Background technology]

[0002] Tumor Treating Field (TT Field) Therapy is a proven approach to treat tumors using alternating electric fields at frequencies between 50 kHz and 1 MHz, more commonly 100-500 kHz. In current commercial systems, the alternating electric field is induced by electrode assemblies (e.g., capacitively coupled electrode arrays, also called transducer arrays) placed on opposite sides of the subject's body. When an alternating voltage is applied between the opposing electrode assemblies, an alternating current flows through the electrode assemblies into the subject's body; and higher currents are strongly correlated with higher therapeutic efficacy.

[0003] Figure 1A is a schematic diagram of a prior art electrode assembly 40 including nine prior art electrode elements labeled X1-X9, and Figure 1B is a cross-sectional schematic diagram of electrode elements X7-X9 of electrode assembly 40 taken along the dashed line in Figure 1A.

[0004] As shown in FIG. 1(B), electrode element X7 (exemplary) includes a metal layer (shown with diagonal hatching) and a ceramic (dielectric) layer. A layer of conductive hydrogel is provided between each ceramic layer and the subject's skin to ensure good electrical contact between the electrode element and the body. An AC voltage from an AC voltage generator (not shown) is applied to the metal layer of the electrode element in the opposing electrode assembly to generate a TT field within the subject's body. An adhesive cover (bandage) is typically provided over the electrode assembly to hold the electrode assembly in place during use.

[0005] During use, the hydrogel and skin beneath the electrode elements heat up, and safety reasons require that the skin temperature be maintained below a safety threshold (e.g., 41° C.). Because the majority of the heat appears beneath the electrode elements X1-X9, prior art electrode assemblies have hot spots beneath the electrode elements and colder regions located between the electrode elements, which in turn limit the amount of current that can be delivered through the prior art electrode assemblies.

[0006] The hydrogel layer(s) of the electrode assembly can also have various problems. For example, hydrogels have a limited shelf life, necessitating moisture-proof packaging, which increases the packaging costs of the electrode assembly. In addition, the signal passing through the hydrogel can vary with the specific water content in the hydrogel, which can fail with too much or too little water. Furthermore, electrode assemblies with hydrogel layers must be replaced frequently during use, and many patients have adverse reactions (e.g., allergic reactions) to the hydrogel. Summary of the Invention [Means for solving the problem]

[0007] The present disclosure relates to electrode assemblies and methods of their use in TT field therapy. In one embodiment, the disclosed device includes at least one electrode element having a skin-facing surface, an anisotropic material layer having an outward-facing surface opposite the skin-facing surface, a first non-hydrogel conductive adhesive layer located between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer, and a skin contact layer comprising a biocompatible conductive adhesive and disposed on the skin-facing side of the anisotropic material layer or, in some embodiments, disposed on the skin-facing surface of the anisotropic material layer. The first non-hydrogel conductive adhesive layer facilitates electrical contact between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer.

[0008] In one embodiment of a method of use, the method includes the steps of positioning at least first and second electrode assemblies on a body of a subject, each of the first and second electrode assemblies including at least one electrode element having a skin-facing surface, an anisotropic material layer having an outward-facing surface opposite the skin-facing surface, a first non-hydrogel conductive adhesive layer positioned between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer, and a skin contact layer including a biocompatible conductive adhesive and disposed on the skin-facing side of the anisotropic material layer, wherein the first non-hydrogel conductive adhesive layer facilitates electrical contact between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer; and applying an alternating voltage between the first electrode assembly and the second electrode assembly to generate an electric field.

[0009] The foregoing summary and the following description of the disclosure can be better understood when read in conjunction with the accompanying drawings. To illustrate the disclosure, the accompanying drawings show some, but not all, alternative embodiments. The disclosure is not limited to the precise arrangements and tools shown. The following drawings, which are incorporated in and constitute a part of the specification, serve to explain the principles of the disclosure. [Brief description of the drawings]

[0010] [Figure 1A] FIG. 1 is a schematic diagram of a prior art electrode assembly. [Figure 1B] FIG. 1B is a cross-sectional view of an electrode element of a prior art electrode assembly taken along the dashed line in FIG. 1A. [Diagram 2] FIG. 1 is a schematic plan view of an electrode assembly including electrode elements used to apply a TT field to a subject's body. [Diagram 3] 3 is a cross-sectional view of the first embodiment including electrode elements E1, E2 taken along the dashed line in FIG. 2. [Figure 4A] 1 is a thermal image of a prior art electrode assembly. [Figure 4B] 4 is a thermal image of an electrode assembly corresponding to the embodiment of FIG. 3. [Figure 4C]4 is a graph comparing thermal properties of a prior art electrode assembly with the embodiment of FIG. 3. [Diagram 5] 3 is a cross-sectional view of a second embodiment including electrode elements E1, E2 taken along the dashed line in FIG. 2. [Figure 6] FIG. 13 is a cross-sectional view of a third embodiment including a single electrode element E1. [Figure 7] FIG. 1 is a block diagram of a system incorporating two electrode assemblies used to apply a TT field to a subject's body. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] A definition When the term "about" precedes a numerical value, unless otherwise specified, the numerical value can vary within ±10%.

[0012] An "anisotropic material" includes any material that has a physical property (eg, a thermal or electrical property) that has different values ​​when measured in different directions.

[0013] The term "non-hydrogel" refers to a material that is not a hydrogel, i.e., a material that does not contain a cross-linked hydrophilic polymer that is insoluble in water.

[0014] "Skin contact layer" means a layer configured to contact the skin of a subject (eg, a TT field is applied by an electrode assembly adhered to the skin of a subject).

[0015] "Subject" refers to any living subject, including a mammalian subject, such as a human.

[0016] "Particle" has a general meaning including very small chunks, pieces or pieces of material. The term "particle" includes, but is not limited to, carbon sheets, carbon particles, carbon fibers, carbon nanotubes, single-walled carbon nanotubes, multi-walled carbon nanotubes, carbon black powder, graphite powder, carbon nanowires, and carbon microcoils.

[0017] The present invention may be more readily understood by reference to the following detailed description, examples, drawings and claims, as well as the accompanying description, but it is to be understood that the invention is not limited to the particular apparatus, devices, systems and / or methods disclosed, unless expressly stated, as such may, of course, vary.

[0018] The names are provided for convenience only and should not be construed as limiting the invention in any manner. Embodiments presented under any heading or in any portion of this disclosure may be combined with embodiments presented under the same or other headings or portions of this disclosure.

[0019] Unless otherwise indicated or clearly contradicted by context, the invention includes any combination of all possible variations of the elements described.

[0020] B Electrode Assembly The present application describes an exemplary electrode assembly that can be used, for example, to deliver a TT field to the body of a subject to treat one or more cancers or tumors present within the subject's body.

[0021] When a TT field is applied to a subject's body, the temperature of the subject's body can increase in proportion to the induced electric field. Regulations limit the amount of current that can be applied to the transducer array to an amount that keeps the temperature measured at each site on the subject's body below a temperature threshold. As practiced in the art, the temperature at the location of the transducer array on the subject's body is controlled below the temperature threshold by reducing the operating current driven by the transducer array and reducing the strength of the resulting TT field. This places a priority limit on the TT field strength that can be used to treat tumors. There is therefore a need in the art to safely obtain higher TT field strengths without exceeding the temperature threshold of the subject's skin.

[0022] In transducer arrays that include multiple electrode elements, the portions of the transducer array located directly under the electrode elements will be hotter than the portions of the transducer array located between the electrode elements. Additionally, in transducer arrays that include multiple electrode elements, more current will flow through electrode elements located along the edges of the array compared to electrode elements located near the center of the array. Additionally, electrode elements located at corners or similar sharp bends at the edges of the array will have higher currents than other electrode elements near the edges and center of the array. The tendency of transducer arrays to pass higher currents through electrode elements located along the edges of the array, especially at corners, is referred to as the "edge effect."

[0023] Uneven distribution of current through the transducer array due to electrode element distribution or edge effects can result in higher temperature regions (or "hot spots"), such as at the corners or edges of the transducer array. These hot spots are the locations that first reach a threshold temperature, thus controlling the requirement to reduce the current. The creation of hot spots therefore limits the maximum operating current that can be driven by the transducer array and the strength of the TT field generated thereby.

[0024] The inventors have now recognized that there is a need for a transducer array that reduces or minimizes uneven distribution of current and allows for the application of higher operating currents. Transducer arrays operating at increased currents can induce stronger TT fields within a subject's body, ultimately improving patient outcomes. The disclosed electrode assemblies allow current and heat to be distributed uniformly throughout the array, thereby minimizing or eliminating hot spots.

[0025] The disclosed embodiments incorporate a sheet of material with anisotropic thermal or electrical properties into the electrode assembly. If the sheet of material has anisotropic thermal properties (e.g., the thermal conductivity in the plane of the sheet is higher than the thermal conductivity perpendicular to the plane of the sheet), the sheet spreads heat more evenly over a larger surface area. If the sheet of material has anisotropic electrical properties (e.g., the electrical conductivity in the plane of the sheet is higher than the electrical conductivity perpendicular to the plane of the sheet), the sheet distributes current more evenly over a larger surface area. In either case, when a predetermined AC voltage is applied to the electrode assembly, the temperature of the hot spots decreases and the temperature of the cooler regions increases (compared to the prior art configurations described above). This allows the current to be increased (and thus the therapeutic effect increased) without exceeding a safe temperature threshold at any point on the subject's skin.

[0026] In some embodiments, the anisotropic material is anisotropic with respect to electrical conductivity. In further embodiments, the anisotropic material is anisotropic with respect to thermal conductivity properties. In certain embodiments, the anisotropic material is anisotropic with respect to both electrical and thermal conductivity properties.

[0027] Anisotropic thermal properties include directional thermal properties. Specifically, the anisotropic material sheet has a first thermal conductivity in a direction perpendicular to its front surface. And, the thermal conductivity of the sheet in a direction parallel to the front surface is at least two times higher than the first thermal conductivity. In some embodiments, the thermal conductivity in the parallel direction is at least ten times higher than the first thermal conductivity. For example, the thermal conductivity of the sheet in a direction parallel to the front surface may be greater than 1.5, 2, 3, 5, 10, 20, 30, 100, 200, or even 1000 times higher than the first thermal conductivity. In some embodiments, the thermal conductivity of the sheet in a direction parallel to the front surface is 1.5 to 1000 times higher than the first thermal conductivity. In some embodiments, the thermal conductivity of the sheet in a direction parallel to the front surface is 1.5 to 20 times higher than the first thermal conductivity. For example, the thermal conductivity of a pyrolytic graphite sheet in the xy plane direction is 10 to 20 times that in the vertical z direction.

[0028] Anisotropic electrical properties include directional electrical properties. Specifically, the sheet has a first resistance in a direction perpendicular to its surface, and a resistance in a direction parallel to the front surface of the sheet is less than the first resistance. In some exemplary embodiments, the resistance in the parallel direction is less than half the first resistance or less than 10% of the first resistance. The electrical resistance of the sheet in the direction parallel to the front surface may be less than 75%, 50%, 40%, 30%, 20%, 10%, 5%, 1%, 0.5%, 0.1%, or even 0.05% of the first resistance. In some embodiments, the resistance of the sheet in the direction parallel to the front surface is between 0.05% and 10% of the first resistance. In some embodiments, the resistance of the sheet in the direction parallel to the front surface is between 0.05% and 10% of the first resistance. For example, the resistivity of a pyrolytic graphite sheet in the xy plane is about three orders of magnitude (1000 times) lower than the resistivity in the perpendicular z direction.

[0029] In some embodiments (eg, when the anisotropic sheet of material is a pyrolytic graphite sheet), the anisotropic sheet of material has anisotropic electrical properties and anisotropic thermal properties.

[0030] In some embodiments (e.g., when the anisotropic material sheet is a pyrolytic graphite sheet), the anisotropic material sheet is non-metallic. These embodiments are particularly advantageous when it is desirable to prevent ion migration into the subject. More specifically, the use of a metallic sheet may result in the migration of metallic ions into the subject's body. In cases where this is undesirable, the non-metallic sheet embodiments using anisotropic material are preferred.

[0031] In addition to the anisotropic material, embodiments of the disclosed electrode assemblies feature a non-hydrogel conductive adhesive layer located between the skin-facing surface of the electrode element and the outwardly facing surface of the anisotropic material layer. Such a top non-hydrogel conductive adhesive improves electrical conductivity in the z-axis direction, i.e., perpendicular to the plane of the anisotropic material layer.

[0032] In general, without being bound by theory, anisotropic materials allow for a voltage difference from the center to the edge of the surface, allowing current flow to be spread more evenly. This reduces the shielding effect (edge ​​effect) and reduces the presence of hot spots in the skin contact layer. However, when current is forced along a narrow area, heat is generated in that area due to the contact resistance between the electrode and the top adhesive layer. The contact area can be increased so that heating due to contact resistance is not a limiting factor, but increasing the area also increases the amount of shielding due to the applied voltage. As previously mentioned, this results in non-uniform temperatures along the skin contact area.

[0033] The inventors have found that by reducing the z-direction resistance of the top adhesive layer, heat generation due to the contact resistance between the electrodes and the top adhesive can be reduced. This can be achieved by introducing a higher dielectric material to the top adhesive layer or by combining materials with increased conductivity in the z-direction. The addition of a dielectric material to the top adhesive layer introduces a capacitive component. As a stronger electric field is generated, the resistivity of the capacitor decreases and approaches zero, increasing the conductivity of the material while minimizing heat generated at the contact between the electrodes and the top adhesive. Conductivity in the z-direction can also be increased by increasing the surface area in the z-direction of the conductive components in the adhesive. For example, structures such as carbon nanowires tend to be flat in a plane and exhibit excellent xy conductivity along the length of the wire. Also, the conductivity in the z-direction of the contact between the wires can be improved to some extent. The function of carbon nanotubes may be similar. It is believed that 3D structures such as carbon microcoils and other shapes with large 3D footprints (in terms of filling the 3D volume) may show enhanced conductivity in the z-direction. Such materials are referred to herein as conductive materials with 3D carbon structures.

[0034] Thus, it is expected that embodiments including anisotropic material sheets will help to avoid or reduce overheating of the electrodes and associated discomfort on the skin by dissipating current and heat laterally (in-plane) rather than concentrating directly through the layer. And, particularly if it is desirable to replace the hydrogel with a non-hydrogel conductive adhesive in this layer, lowering the z-resistance of the top adhesive layer can reduce heat generated from the contact resistance between the electrodes and the top adhesive layer, further enabling the realization of the beneficial effect of providing higher operating currents at a selected temperature (e.g., keeping below a threshold temperature of about 41° C., or choosing to run at a maximum skin surface temperature of 38-41° C., or about 38-40° C.).

[0035] FIG. 2 is a schematic diagram of an embodiment of an electrode assembly 50 including electrode elements for applying a TT field to a subject's body. In FIG. 2, only two electrode elements, labeled E1 and E2, are shown, but additional electrode elements may be included in the electrode assembly 50. In another embodiment, the electrode assembly 50 includes only a single electrode element. It is noted that FIG. 2 illustrates the electrode assembly 50 in a schematic manner, and that these electrode assemblies E1 and E2 may have different configurations (e.g., as described below in connection with FIGS. 3-7).

[0036] FIG. 3 is a cross-sectional view of a first embodiment of an electrode assembly 50a including electrode elements E1, E2 along the dashed line of FIG. 2. In the embodiment of FIG. 3, the electrode assembly 50a includes an anisotropic material sheet 70 having a front surface (directed toward the subject's skin in FIG. 3) and a rear surface. The sheet 70 has a first thermal conductivity in a direction perpendicular to the front surface. The thermal conductivity of the sheet 70 in a direction parallel to the front surface can be more than two times greater than the first thermal conductivity. In some embodiments, the thermal conductivity of the sheet 70 in a direction parallel to the front surface is more than ten times greater than the first thermal conductivity. The sheet 70 of the embodiment of FIG. 3 is also anisotropic in other respects. More specifically, the sheet 70 has a first resistance in a direction perpendicular to the front surface, and the resistance of the sheet in a direction parallel to the front surface can be less than half of the first resistance. In certain embodiments, the resistance of the sheet in a direction parallel to the front surface is less than 10% of the first resistance.

[0037] In some embodiments, the anisotropic material sheet 70 is a pyrolytic graphite sheet (such as pyrolytic graphite sheet (PGS) available from Panasonic Industries, Ltd., Kadoma, Osaka, Japan). The thermal conductivity of the pyrolytic graphite sheet in a direction parallel to its front surface (i.e., in the xy plane) is typically 50 times higher than the thermal conductivity in a direction perpendicular to its front surface (i.e., in the z direction). The electrical resistivity of the pyrolytic graphite sheet in a direction parallel to its front surface (i.e., in the xy plane) is typically less than 2% of the electrical resistivity in a direction perpendicular to its front surface (i.e., in the z direction).

[0038] In other embodiments, the anisotropic material sheet 70 is a graphite foil made of compressed high purity exfoliated mineral graphite (e.g., MinGraph® 2010A flexible graphite, available from Mineral Seal Corp., Tucson, Arizona, USA) or a graphitized polymer film (e.g., graphitized polyimide film) (including but not limited to those provided by Kaneka Corp., Moka, Tochigi, Japan). In other embodiments, the anisotropic material may be pyrolytic carbon. In other embodiments, the anisotropic material may be boron nitride. Other embodiments may utilize other conductive material sheets having anisotropic properties. In some embodiments (e.g., when the anisotropic material sheet is a synthetic graphite sheet such as pyrolytic graphite or compressed high purity exfoliated mineral graphite), the anisotropic material sheet 70 is non-metallic.

[0039] The electrode assembly 50a further includes a biocompatible conductive adhesive material surface layer 60 disposed on the front surface of the sheet 70. The material surface layer 60 may be configured to ensure good electrical contact between the device and the body. In some embodiments, the material surface layer 60 should cover the entire front surface of the anisotropic material sheet 70. The material surface layer 60 may be as large or larger (i.e., of the same area or larger) as the anisotropic material sheet 70. In some embodiments, the conductive material surface layer 60 does not include water. In certain embodiments, the conductive material surface layer 60 is a non-hydrogel conductive material. In other embodiments, the conductive material surface layer 60 includes a hydrogel. In these embodiments, the hydrogel may be between about 20-2000 μm thick, such as 100-1000 μm, or 300-500 μm thick. In some embodiments, the conductive material surface layer 60 is a non-hydrogel biocompatible conductive adhesive. In some embodiments, the surface layer of the conductive material 60 is a non-hydrogel biocompatible conductive adhesive, such as the development product FLX068983-FLEXcon® OMNI-WAVE® TT 200 BLACK H-502 150 POLY H-9 44PP-8 (FLEXcon, Spencer, MA, USA), or other similar OMNI-WAVE products of FLEXcon, or the ARcare® 8006 conductive adhesive composition manufactured and sold by Adhesives Research, Inc. (Glen Rock, PA, USA). The non-hydrogel conductive adhesive may include an anhydride polymer having adhesive properties and carbon particles, powders, fibers, flakes, nanotubes, nanowires, microcoils. The binder polymer may be, for example, an acrylic-based polymer or a silicone-based polymer, or a combination thereof, and may be obtained as an acrylic-based or silicone-based carbon-filled adhesive tape. The adhesive may also include one or more conductive polymers (e.g., polyaniline (PANI), poly(3,4-ethyldioxythiophene (PEDOT), or other polymers known in the art). The conductive fillers of the conductive material surface layer 60 are preferably non-metallic.In these embodiments, the biocompatible conductive adhesive may be between 10 and 2000 μm, for example between 20 and 1000 μm, or between 30 and 400 μm.

[0040] In the embodiment of FIG. 3 (or the embodiments shown in FIGS. 4-7), the surface or skin contact layer of the electrode assembly does not include a latex rubber polymer. In some embodiments, the surface or skin contact layer does not include silver or silver chloride. In additional embodiments, the surface or skin contact layer is releasably bonded to the anisotropic material layer. In these embodiments, the skin contact layer may be selectively separated from the anisotropic material and replaced with a new skin contact layer (e.g., when a maximum / threshold usage duration is near or has been met).

[0041] In certain embodiments, the surface layer or skin contact layer can include a biocompatible conductive adhesive having a thickness range of about 20 mm to about 2000 mm (e.g., about 30 mm to about 2000 mm, e.g., about 30 mm to about 70 mm) or about 45 mm to about 55 mm.

[0042] Alternatively, in exemplary embodiments, the device may further include a release liner covering the skin contact layer. In these embodiments, it is expected that the device will include a release liner to ensure that the skin contact layer does not adhere to undesirable surfaces or locations prior to use. Immediately prior to use, the release liner can be removed and the skin contact layer can be placed in contact with the patient's skin.

[0043] The electrode assembly 50a further includes a first electrode element E1 located rearwardly of the sheet 70. The first electrode element E1 has a first front surface disposed in electrical contact with the rear surface of the sheet 70. In the embodiment of Figure 3, the first electrode element E1 includes a first dielectric (e.g., ceramic) material layer 310 having a front surface and a rear surface, and a first metal layer 320 disposed on the rear surface of the first dielectric material layer 310. The front surface of the first dielectric material layer 310 is the first front surface of the first electrode element E1.

[0044] The dielectric material need not be ceramic. In some aspects, for example, the dielectric material 310 can include a polymer (e.g., a high dielectric constant polymer). Thus, in all embodiments disclosed herein, it should be understood that the dielectric material 310, shown in the drawings as ceramic, can be any suitable dielectric material (e.g., a polymer layer having a dielectric constant of at least 10, or another material having a dielectric constant of at least 10).

[0045] In some embodiments, the dielectric material layer 310 can have a dielectric constant in the range of 10 to 50,000. In some embodiments, the dielectric material layer 310 comprises a highly dielectric polymeric material such as poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) and / or poly(vinylidene fluoride-trifluoroethylene-1-chlorofluoroethylene). These two polymers are abbreviated herein as "poly(VDF-TrFE-CTFE)" and "poly(VDF-TrFE-CFE)", respectively. These embodiments are particularly advantageous since the dielectric constant of these materials is about 40. In some embodiments, the polymeric layer may be poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene-chlorofluoroethylene) or "poly(VDF-TrFE-CTFE-CFE)".

[0046] In some embodiments, the dielectric material layer 310 includes a terpolymer including polymerized units of any suitable molar ratio of monomers such as VDF, TrFE, CFE, and / or CTFE. Suitable terpolymers include, for example, those having 30-80 mol % VDF, 5-60 mol % TrFE, with CFE and / or CTFE making up the remainder of the mol % of the terpolymer.

[0047] In some embodiments, the sheet 70 has a center of gravity, and the center of gravity of the first front surface of the first electrode element E1 is located at a distance of less than 3 cm from the center of gravity of the sheet 70. In some embodiments, the sheet 70 has a center of gravity and a dimension (e.g., length or width) parallel to the rear surface of the sheet 70, and the center of gravity of the first front surface of the first electrode element E1 is located at a distance of less than 30% or less than 10% of the dimension from the center of gravity of the sheet 70.

[0048] The electrode assembly 50a further includes a first non-hydrogel conductive adhesive layer 80 between the first front surface of the first electrode element E1 (i.e., the front surface of the first dielectric material layer 310) and the rear surface of the sheet 70. The first non-hydrogel conductive adhesive layer 80 facilitates electrical contact between the first front surface of the first electrode element E1 and the rear surface of the sheet 70. In the illustrated embodiment, the conductive material layer 80 is a non-hydrogel conductive adhesive layer. In some embodiments, a different conductive material (e.g., conductive grease, conductive adhesive, conductive tape, etc.) can be used. In some embodiments, the non-hydrogel conductive adhesive layer 80 is a non-hydrogel biocompatible conductive adhesive, such as the development product FLX068983-FLEXcon® OMNI-WAVE® TT 200 BLACK H-502 150 POLY H-9 44PP-8 (FLEXcon, Spencer, MA, USA), or other similar OMNI-WAVE products from FLEXcon, or the ARcare® 8006 conductive adhesive composition manufactured and sold by Adhesives Research, Inc. (Glen Rock, PA, USA). The non-hydrogel conductive adhesive may include an anhydride polymer having adhesive properties. The binder polymer may be, for example, an acrylic-based polymer, a silicone-based polymer, or a combination thereof. In these embodiments, the first layer of conductive adhesive may be between 10 and 2000 μm thick, such as between 20 and 1000 μm, or between 30 and 400 μm.

[0049] In some embodiments, the electrode assembly 50a or other electrode assemblies are characterized by a first non-hydrogel conductive adhesive layer that includes a material that promotes electrical conductivity in a direction perpendicular to the plane of the anisotropic material layer (z-direction). The non-hydrogel conductive adhesive can include an anhydrous polymer with adhesive properties and carbon particles, powders, fibers, flakes, nanotubes or nanowires, or a combination thereof. In some embodiments, the non-hydrogel conductive adhesive includes conductive particles with a three-dimensional structure and a shape with a significant three-dimensional footprint (for a filled three-dimensional volume) to enhance electrical conductivity in the z-direction, such as carbon microcoils. The binder polymer can be, for example, an acrylic-based polymer or a silicone-based polymer, or a combination thereof, and can be obtained as an acrylic-based or silicone-based carbon-filled adhesive tape. The adhesive can also include one or more conductive polymers, such as polyaniline (PANI), poly(3,4-ethyldioxythiophene (PEDOT), or other polymers known in the art. The conductive fillers in the first conductive material layer 80 can be non-metallic.

[0050] The electrode assembly 50a may optionally include one or more additional electrode elements. In the illustrated embodiment, the electrode assembly 50a includes a second electrode element E2 located behind the sheet 70. The second electrode element E2 has a second front surface disposed in electrical contact with the rear surface of the sheet 70. The two electrode elements E1, E2 in FIG. 3 have the same structure. Thus, the second electrode element E2 includes a second dielectric (e.g., ceramic) material layer 310 having a front surface and a rear surface, and a second layer of metal 320 disposed on the rear surface of the second dielectric material layer 310. The front surface of the second dielectric material layer 310 is the second front surface of the second electrode element E2.

[0051] The first non-hydrogel conductive adhesive layer 80 is located between the second front surface of the second electrode element E2 (i.e., the front surface of the second dielectric material layer 310) and the rear surface of the sheet 70. The first non-hydrogel conductive adhesive layer 80 facilitates electrical contact between the second front surface of the second electrode element E2 and the rear surface of the sheet 70. As described for E1 and shown in FIG. 3, the conductive material 80 may be a layer of a non-hydrogel material, e.g., a material that does not contain water in some embodiments. In some embodiments, different conductive materials (e.g., conductive grease, conductive adhesives including the non-hydrogel conductive adhesives described above, conductive tape, conductive composites, etc.) may be used.

[0052] The metal layers 320 of all the electrode elements (i.e., E1 and E2 in the illustrated embodiment) may be wired together (e.g., using wires, traces on a flexible substrate, etc.) to a lead 90. The lead 90 supplies an AC voltage from an AC voltage generator (not shown) to the electrode elements to generate a TT field when the electrode assembly 50a is secured to the subject's body for treatment.

[0053] Alternatively, the electrode assembly 50a may include a flexible self-adhesive backing 55 configured to support the sheet 70, the first electrode element E1 (and any other electrode elements present in the electrode assembly), and the biocompatible conductive material surface layer 60, which may be placed against the subject's skin.

[0054] In some embodiments, the use of a biocompatible conductive layer as the skin contact layer is expected to omit an additional backing and / or cover layer (e.g., self-adhesive backing 55) (for any of the embodiments shown in Figures 3-7). In these embodiments, the biocompatible conductive layer can provide sufficient adhesion to the skin, eliminating the need for an additional layer to hold the electrode assembly in a desired position on the subject's body, thereby improving ease of use and reducing the overall cost of manufacture and use.

[0055] The superior performance of the embodiment of FIG. 3 is illustrated in FIGS. 4A, 4B, and 4C. FIG. 4A is a thermal image of a prior art electrode assembly (see, e.g., FIG. 1B) that includes two electrode elements and a hydrogel layer disposed on the front surface of the electrode elements. There is no anisotropic material sheet between the front surface of the electrode elements and the rear surface of the hydrogel layer. In use, the front surface of the hydrogel layer rests on the subject's skin. FIG. 4A shows hot spots occurring in the areas corresponding to the electrode elements.

[0056] FIG. 4B is a thermal image of an electrode assembly corresponding to the embodiment of FIG. 3, in which pyrolytic graphite was used as the anisotropic material. FIG. 4B shows that hot spots, as produced by the prior art electrode assembly, are minimized and the maximum temperature is reduced. FIG. 4C is a graph comparing the thermal performance of the embodiment of FIG. 3 (using pyrolytic graphite as the anisotropic material) with the prior art (without anisotropic material) for the same applied current (500 mA). Note that the hottest part of the prior art electrode assembly was 41° C. However, when the same 500 mA current is applied to the embodiment of FIG. 3, the hottest part of the electrode assembly is only 32° C. Similar experiments were performed using graphite foil compressed with high purity exfoliated mineral graphite as the anisotropic material, with similar results.

[0057] In related experiments, an optimized conventional array (without anisotropic material) is limited as it operates at 2 A applied current and operates at an average temperature of up to 40°C. The same type of array with added pyrolytic graphite sheets (as in the embodiment of FIG. 3) can be operated at increased power levels (3 A current applied) and operates at an average temperature of 38°C, 2-3°C below the temperature threshold limit. This result suggests that the inventive apparatus and methods described herein should be able to achieve more beneficial treatment results by operating at higher applied currents while maintaining the temperature of the skin surface below the threshold temperature (approximately 41°C).

[0058] FIG. 5 is a cross-sectional view of a second embodiment of an electrode assembly 50b including electrode elements E1, E2 along the dashed line of FIG. 2. The embodiment of FIG. 5 is similar to the embodiment of FIG. 3 in all respects, except as follows: the embodiment of FIG. 3 includes a large continuous layer of non-hydrogel conductive adhesive material 80 between the sheet 70 and the front faces of the first and second electrode elements E1, E2. The embodiment of FIG. 5, on the other hand, includes individual areas of non-hydrogel conductive adhesive material 380 (abbreviated "NHCA") for each individual electrode element. Thus, the embodiment of FIG. 5 includes a first non-hydrogel conductive adhesive material layer 380 between the first front face of the first electrode element E1 and the rear face of the sheet 70, and further includes a second non-hydrogel conductive adhesive material layer 380 between the second front face of the second electrode element E2 and the rear face of the sheet 70. The first non-hydrogel conductive adhesive material layer and the second non-hydrogel conductive adhesive material layer 380 contribute to electrical contact between the front and rear faces of each electrode of the sheet 70. 5, the non-hydrogel conductive adhesive material layer 380 is a layer of material that is free of hydrogel in certain embodiments and free of water in some aspects. In other embodiments, the non-hydrogel conductive adhesive material 70 can include conductive particles such as three-dimensional carbon structures to enhance electrical conductivity in the z-direction, as described above and elsewhere herein. In some embodiments, different conductive materials can be used (e.g., conductive grease, conductive adhesives including the non-hydrogel conductive adhesives described above, conductive tapes, conductive composites, etc.).

[0059] As with the embodiment of FIG. 3, the current in the embodiment of FIG. 5 is still concentrated in the non-hydrogel conductive adhesive material top layer 380 only in the area under the electrode elements. The anisotropic material sheet 70 distributes heat and current as described above in connection with the embodiment of FIG. 3, eliminating or at least minimizing hot spots. This means that for a given applied AC voltage, the hottest point under the electrode assembly in the embodiment of FIG. 5 will be at a lower temperature than the hottest point under the electrode assembly in the prior art of FIG. 1. Thus, in the embodiment of FIG. 5, the current can be increased (relative to the current in the prior art) at any point under the electrode assembly without exceeding a safe temperature threshold. Such an increase in current advantageously increases the effectiveness of the TT field treatment.

[0060] FIG. 6 is a cross-sectional view of a third embodiment of an electrode assembly 50c including a single electrode element E1. The embodiment of FIG. 6 is similar to the embodiment of FIG. 3, except that it does not include a dielectric material layer. In the embodiment of FIG. 6, the electrode assembly 50c includes an anisotropic material sheet 70 having a front surface (which is directed toward the subject's skin in FIG. 6) and a rear surface. The sheet 70 is similar to the sheet 70 described above in connection with FIG. 3. In certain embodiments, the anisotropic material sheet 70 is a synthetic graphite sheet. In certain embodiments, the anisotropic material sheet 70 is a pyrolytic graphite sheet. In other embodiments, the anisotropic material sheet 70 is a pyrolytic carbon sheet. In other embodiments, the anisotropic material sheet 70 is a graphite foil made of compressed high-purity exfoliated mineral graphite (e.g., MinGraph® 2010A soft graphite). In other embodiments, the anisotropic material may be boron nitride. In other embodiments, the anisotropic material sheet 70 is another conductive anisotropic material sheet.

[0061] The electrode assembly 50c further includes a biocompatible conductive material surface layer 60 disposed on the front surface of the sheet 70. The conductive material surface layer 60 is configured to ensure good electrical contact between the device and the body. In one embodiment, the conductive material surface layer 60 should cover the entire front surface of the anisotropic material sheet 70. The conductive material surface layer 60 may be as large or larger (i.e., of the same area or larger) as the anisotropic material sheet 70. In some embodiments, the conductive material surface layer includes a non-hydrogel conductive material, including, for example, a conductive material that does not include water. In other embodiments, the conductive material surface layer 60 includes a hydrogel. In these embodiments, the hydrogel may be between 20-2000 μm thick, for example, 50-1000 μm, or 100-500 μm thick. In some embodiments, the conductive material surface layer 60 is a non-hydrogel biocompatible conductive adhesive, as described above, including OMNI-WAVE® products from FLEXcon, or ARcare® products from Adhesives Research, Inc. The non-hydrogel conductive adhesive may include an adhesive anhydride polymer (e.g., an acrylic polymer or a silicone polymer, or a combination thereof) and a conductive filler. The conductive filler of the conductive material surface layer 60 should be non-metallic. In these embodiments, the biocompatible conductive adhesive may be 10-2000 μm, such as 20-1000 μm, or 30-400 μm.

[0062] The electrode assembly 50c further includes a first electrode element E1 located behind the sheet 70. The first electrode element E1 includes a metal plate 500 having a front surface arranged to be in electrical contact with the rear surface of the sheet 70. In the embodiment of FIG. 6, the front surface of the metal plate 500 is the first front surface of the first electrode element E1. The embodiment of FIG. 6 thus differs from the embodiment of FIG. 3A or FIG. 5 by omitting the dielectric material layer. In this embodiment of FIG. 6, the positional relationship between the first electrode element E1 and the sheet 70 can be as described above in connection with FIG. 3.

[0063] The electrode assembly 50c further includes a first non-hydrogel conductive adhesive material layer 80 between the first front surface of the first electrode element E1 (i.e., the front surface of the metal sheet 500) and the rear surface of the sheet 70. The first non-hydrogel conductive adhesive material layer 80 facilitates electrical contact between the first front surface of the first electrode element E1 and the rear surface of the sheet 70. In the illustrated embodiment, the non-hydrogel conductive adhesive material layer 80 is a material layer that does not include hydrogel in certain embodiments and does not include water in some aspects. In other embodiments, the non-hydrogel conductive adhesive material 80 can include conductive particles such as three-dimensional carbon structures to enhance electrical conductivity in the z-direction as described above. In some embodiments, different conductive materials (e.g., conductive grease, conductive adhesives including the non-hydrogel conductive adhesives described above, conductive tapes, conductive composites, etc.) can be used.

[0064] The metal strips 500 of the electrode element E1 are wired (e.g., using wires, traces on a flexible substrate, etc.) to a lead 90 that supplies an AC voltage from an AC voltage generator (not shown) to the electrode elements, and a TT field is generated when the electrode assembly 50c is applied to the subject's body for treatment. The electrode assembly 50c can optionally include one or more additional electrode elements having the same structure as the electrode element E1 and arranged to have the same function. In such a case, the metal strips 500 of all the electrode elements can be wired together (e.g., using wires, traces on a flexible substrate, etc.) to the lead 90.

[0065] In some embodiments including only a single electrode element E1, the area of ​​sheet 70 is greater than the area of ​​electrode element E1 (e.g., at least two times, or at least four times, or at least ten times). In some embodiments including multiple electrode elements (not shown), the area of ​​sheet 70 is greater than the combined area of ​​all the electrode elements (e.g., at least two times, four times, or ten times greater). When an AC voltage is applied to the electrode elements, heat spreads throughout sheet 70, minimizing or eliminating hot spots.

[0066] As with the embodiment of FIG. 3, the anisotropic material sheet 70 in the embodiment of FIG. 6 distributes heat and current as described above in connection with the embodiment of FIG. 3, eliminating or at least minimizing hot spots. This means that for a given applied AC voltage, the hot spots under the electrode assembly in the embodiment of FIG. 6 have a lower temperature than the hot spots under the electrode assembly in the prior art embodiment of FIG. 1. Thus, in the embodiment of FIG. 6, the current can be increased (relative to the current in the prior art) at any point under the electrode assembly without exceeding a safe temperature threshold. Such an increase in current advantageously increases the effectiveness of the TT field treatment.

[0067] FIG. 7 illustrates a method of applying an AC electric field to a target region within a subject's body using a pair of electrode assemblies 50a of FIG. 3. (Note that any of the electrode assemblies described above in connection with FIGS. 3-6 may be used in place of the electrode assembly 50a of FIG. 3 illustrated here). The method includes placing a first electrode assembly 50a at a first location on or within the subject's body. (In the example illustrated in FIG. 7, the first electrode assembly 50a is placed on the subject's skin on the right side of the subject's head facing the target region, e.g., a tumor.) The first electrode assembly 50a may be configured as previously described. In the embodiment of FIG. 7, the first electrode assembly 50a includes a first sheet 70 of anisotropic material having a first front surface and a first rear surface. The first sheet 70 has a first thermal conductivity in a direction perpendicular to the first front surface. The thermal conductivity of the first sheet 70 in a direction parallel to the first front surface is at least twice the first thermal conductivity. The first sheet 70 has a first resistance in a direction perpendicular to the front surface and the resistance of the first sheet in a direction parallel to the front surface is less than half the first resistance. In use, the first electrode assembly 50a is positioned such that the first front surface of the first sheet 70 faces the target area.

[0068] The method further includes placing the second electrode assembly 50a at a second location in or on the subject's body (in the example shown in FIG. 7, the second electrode assembly 50a is placed on the subject's skin on the left side of the subject's head facing the target area). The second electrode assembly 50a may be configured as described herein. In the embodiment of FIG. 7, the second electrode assembly 50a includes a second sheet 70 of anisotropic material 70 having a second front surface and a second rear surface. The second sheet 70 has a second thermal conductivity in a direction perpendicular to the second front surface. The thermal conductivity of the second sheet 70 in a direction parallel to the second front surface is equal to or greater than twice the second thermal conductivity. The second sheet 70 has a second resistance in a direction perpendicular to the front surface, and the resistance of the second sheet in a direction parallel to the front surface is equal to or less than half the second resistance. In use, the second electrode assembly 50a is positioned such that the second front surface of the second sheet 70 faces the target area.

[0069] An AC voltage is applied between the first electrode assembly 50a and the second electrode assembly 50a. The application is performed after the first electrode assembly 50a and the second electrode assembly 50a are arranged. The application can be performed by applying an AC voltage between (i) a first electrode element arranged in electrical contact with the first rear surface of the first sheet 70, and (ii) a second electrode element arranged in electrical contact with the second rear surface of the second sheet 70.

[0070] In some embodiments, the first electrode assembly 50a further includes a first layer of biocompatible conductive material 60 disposed on the first front surface of the first sheet 70. Accordingly, the second electrode assembly further includes a second layer of biocompatible conductive material 60 disposed on the second front surface of the second sheet 70. As discussed above, the biocompatible conductive material 60 may be a hydrogel, a conductive grease, a conductive adhesive, including the non-hydrogel conductive adhesives described above, a conductive tape, a conductive composite material, or the like.

[0071] In some embodiments, the first electrode assembly 50a further includes a first non-hydrogel conductive adhesive top layer 80 (as described above) between the first front (skin-facing) surface of the first electrode element of the first electrode assembly 50a and the first rear (outer-facing) surface of the first sheet 70, such that the first electrode element of the first electrode assembly is in electrical contact with the outer-facing surface of the sheet 70. Accordingly, the second electrode assembly further includes a second non-hydrogel conductive adhesive top layer 80 (as described above) between the second front (skin-facing) surface of the second electrode element of the second electrode assembly and the second rear surface of the second sheet 70, such that the second electrode element of the second electrode assembly is in electrical contact towards the outer surface of the sheet 70.

[0072] In certain embodiments, each of the first and second anisotropic material sheets 70 is a synthetic graphite sheet. In certain embodiments, each of the first and second anisotropic material sheets 70 is a pyrolytic graphite sheet. In other embodiments, each of the first and second anisotropic material sheets 70 is a graphite foil made of compressed high purity exfoliated mineral graphite or graphitized polymer film sheets. In other embodiments, the anisotropic material may be pyrolytic carbon. In other embodiments, the anisotropic material may be boron nitride. Other embodiments may utilize other conductive material sheets having anisotropic properties. In some embodiments (e.g., when the anisotropic material sheet is a synthetic graphite sheet such as pyrolytic graphite or compressed high purity exfoliated mineral graphite), the anisotropic material sheet 70 is non-metallic.

[0073] The AC voltage between the first and second electrode assemblies can be applied by an AC voltage generator 820. In some embodiments, the frequency of the AC 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 controller 822. The controller 822 can control the magnitude of the current delivered through the first and second electrode assemblies 50a by temperature measurement to maintain the temperature below a safety threshold (e.g., 41° C.). This can be accomplished, for example, by measuring a first temperature of the first electrode element, measuring a second temperature of the second electrode element, and controlling the application of the AC voltage based on the first and second temperatures, as follows:

[0074] 7 shows an example of suitable hardware for this purpose. More specifically, a temperature sensor 800 (e.g., a thermistor) is positioned in thermal contact with a corresponding electrode element (e.g., dielectric material 310 / metal layer 320) in each electrode assembly 50a. The temperature sensor 800 measures corresponding first and second temperatures (e.g., the first and second electrode elements of the first and second electrode assemblies, respectively), and a controller 822 controls the output of an AC voltage generator 820 based on these temperatures.

[0075] Similar embodiments and methods are envisioned utilizing any or combination of the electrode assemblies 50a-e in place of one or both of the first and second electrode assemblies 50a, 50a.

[0076] C. Non-hydrogel conductive adhesive top layer For any embodiment, the non-hydrogel conductive adhesive top layer (e.g., layer 80 in Figures 3, 6, and 7, and layer 380 in Figure 5) can comprise any suitable conductive material that does not include a hydrogel, whereby the electrode element(s) of the electrode assembly are in electrical contact with the outwardly facing surface of the anisotropic material layer. In some embodiments, the non-hydrogel conductive adhesive layer does not include water.

[0077] In an exemplary embodiment, the non-hydrogel conductive adhesive layer can include a dielectric material and conductive particles dispersed within the dielectric material. In some such embodiments, at least a portion of the conductive particles can define a conductive path through the thickness of the non-hydrogel conductive adhesive layer. In some embodiments, the conductive particles are expected to position in response to application of an electric field such that the conductive particles undergo electrophoresis. In some embodiments, the dielectric material of the non-hydrogel conductive adhesive layer of each of the first and second electrode assemblies is a polymeric adhesive. Alternatively, the polymeric binder may be an acrylic-based binder or a silicone-based binder.

[0078] In some embodiments, the conductive particles may include carbon in elemental (i.e., non-organic) form. Alternatively, the conductive particles may include graphite powder. Alternatively or additionally, the conductive particles may include carbon flakes. Alternatively or additionally, the conductive particles may include carbon particles. Alternatively or additionally, the conductive particles may include carbon fibers. Alternatively or additionally, the conductive particles may include carbon nanotubes. Alternatively or additionally, the conductive particles may include carbon black powder. Alternatively or additionally, the conductive particles may include carbon nanowires. Alternatively or additionally, the conductive particles may include carbon microcoils. In some embodiments, the conductive particles may include graphite powder, carbon black powder, carbon flakes, carbon particles, carbon fibers, carbon nanotubes, graphene nanotubes, single-walled carbon nanotubes, multi-walled carbon nanotubes, carbon nanowires, carbon microcoils, or any combination of these particles.

[0079] In exemplary embodiments, the conductive particles of the non-hydrogel conductive adhesive layer include a plurality of conductive particle populations, in which at least a portion of some or all of the conductive particles of the conductive particle populations are aligned to define a conductive path through the thickness of the non-hydrogel conductive layer of each of the first and second electrode assemblies.

[0080] In some embodiments, the thickness of the non-hydrogel conductive adhesive layer of the electrode assembly ranges from about 20 μm to about 2000 μm, such as from about 30 μm to about 1000 μm, or from about 30 μm to about 70 μm. For example, the non-hydrogel conductive adhesive layer may have a thickness of about 45 μm to about 55 μm.

[0081] In a further embodiment, the non-hydrogel conductive adhesive layer further comprises a polar material (e.g., a polar salt). The polar salt may be a quaternary ammonium salt, such as a tetraalkylammonium salt. Exemplary non-hydrogel conductive adhesive materials, and methods for making such materials, are disclosed in U.S. Pat. Nos. 8,673,184 and 9,947,432, which are incorporated herein by reference for all purposes, including the teachings of non-hydrogel conductivity. In an exemplary embodiment, the non-hydrogel conductive adhesive material may be a dry carbon / salt adhesive, such as the OMNI-WAVE adhesive composition manufactured and sold by FLEXCON (Spencer, MA, USA).

[0082] The non-hydrogel conductive adhesive layer may be a free-standing single layer of conductive adhesive material, or may be present in the form of a tape, double-sided tape, or a scrim or mesh layer having the non-hydrogel conductive adhesive material on one or both sides of the scrim or mesh layer, in which case the adhesive layers on either side of the scrim or mesh can interdiffuse through the interstices of the scrim or mesh, thereby forming a continuous pathway through the scrim or mesh layer.

[0083] For all embodiments disclosed herein, the surface (skin contact) layer of biocompatible conductive adhesive material may be a hydrogel or non-hydrogel conductive adhesive as described above, facilitating electrical contact of the anisotropic material layer to the skin.

[0084] In other aspects, by avoiding the use of hydrogels in the top conductive layer, particularly in the top conductive layer and the surface (skin contact) layer of the biocompatible conductive adhesive material, the electrode assembly including the conductive adhesive material is expected to not require moisture-proof packaging and the cost of packaging is more tolerable. Furthermore, the conductive adhesive material of the disclosed electrode assembly is expected to avoid the signal variation problem of hydrogels and provide consistent material properties (e.g., adhesion) and reliable performance during delivery of the TT field. Furthermore, it is believed that the disclosed conductive adhesive composite has a much longer shelf life than hydrogel-containing materials, reducing the frequency with which the electrode assembly (or the skin contact layer of the electrode assembly) must be replaced.

[0085] D. EXEMPLARY EMBODIMENTS In a first exemplary embodiment, the device includes: (a) at least one electrode element having a skin-facing surface; (b) an anisotropic material layer having an outward-facing surface opposite the skin-facing surface; (c) a first non-hydrogel conductive adhesive layer located between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer; and (d) a skin contact layer comprising a biocompatible conductive adhesive and disposed on the skin-facing side of the anisotropic material layer. In this embodiment, the first non-hydrogel conductive adhesive layer facilitates electrical contact between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer. In some embodiments, the skin contact layer is disposed on the skin-facing surface of the anisotropic material layer.

[0086] In a second exemplary embodiment of the device of the first exemplary embodiment, the biocompatible conductive adhesive of the skin contact layer may include a hydrogel. In a third exemplary embodiment of the device of the first exemplary embodiment, the biocompatible conductive adhesive of the skin contact layer is a water-free non-hydrogel conductive adhesive.

[0087] In a fourth exemplary embodiment of the device of the third exemplary embodiment, the non-hydrogel conductive adhesive of the skin contact layer is different from the non-hydrogel conductive adhesive of the first non-hydrogel conductive adhesive layer.

[0088] In a fifth exemplary embodiment of the device of any of the above exemplary embodiments, the first non-hydrogel conductive adhesive layer does not include water.

[0089] In a sixth exemplary embodiment of the device of any of the above exemplary embodiments, the first non-hydrogel conductive adhesive layer comprises a material that promotes electrical conductivity in the z-direction perpendicular to the plane of the anisotropic material layer.

[0090] In a seventh exemplary embodiment of the device of any of the above exemplary embodiments, the first non-hydrogel conductive adhesive layer includes: (a) a dielectric material; and (b) conductive particles dispersed in the dielectric material. In one embodiment, at least a portion of the conductive particles define a conductive path through a thickness of the first non-hydrogel conductive adhesive layer.

[0091] In an eighth exemplary embodiment of the apparatus of the seventh exemplary embodiment, the conductive particles include an elemental non-organic form of carbon.

[0092] In a ninth exemplary embodiment of the device of the seventh or eighth exemplary embodiment, the conductive particles include carbon flakes, carbon particles, carbon fibers, carbon nanotubes, single-walled carbon nanotubes, multi-walled carbon nanotubes, carbon black powder, graphite powder, carbon nanowires, carbon microcoils, or any combination thereof.

[0093] In a tenth exemplary embodiment of the apparatus of the sixth exemplary embodiment, the material that promotes electrical conductivity in the z-direction perpendicular to the plane of the anisotropic material layer is a conductive material having a three-dimensional carbon structure.

[0094] In an eleventh exemplary embodiment of the device of the tenth exemplary embodiment, the material that promotes electrical conductivity in the z-direction is a carbon microcoil.

[0095] In a twelfth exemplary embodiment of the device of the third exemplary embodiment, the skin contact layer of the non-hydrogel conductive adhesive does not include a three-dimensional carbon structure.

[0096] In a thirteenth exemplary embodiment of the device of any of the above exemplary embodiments, either the first non-hydrogel conductive adhesive layer or the biocompatible conductive adhesive of the skin contact layer, or both, further comprise a polar material.

[0097] In a fourteenth exemplary embodiment of the apparatus of any of the above exemplary embodiments, the anisotropic material layer has a first thermal conductivity in a direction perpendicular to the plane of the layer, and the thermal conductivity in a direction parallel to the plane of the layer is at least two times higher than the first thermal conductivity.

[0098] In a fifteenth exemplary embodiment of the device of any of the first to fourteenth exemplary embodiments, the anisotropic material layer has a first resistance in a direction perpendicular to the plane of the layer, and a resistance in a direction parallel to the plane of the layer that is less than half of the first resistance.

[0099] In a sixteenth exemplary embodiment of the device of any of the sixth to ninth exemplary embodiments, the dielectric material is a polymer binder.

[0100] A seventeenth exemplary embodiment includes an electrode assembly including: (a) at least one electrode element having a skin-facing surface; and (b) at least one non-hydrogel conductive adhesive layer located on the skin-facing side of the at least one electrode element and in electrical contact with the skin-facing surface of the at least one electrode element. In this exemplary embodiment, the at least one non-hydrogel conductive adhesive layer includes one or more dielectric polymers and conductive particles having a three-dimensional carbon structure for enhancing electrical conductivity in a z-direction perpendicular to the plane of the non-hydrogel conductive adhesive layer.

[0101] In an eighteenth exemplary embodiment of the electrode assembly of the seventeenth exemplary embodiment, the conductive particles having a three-dimensional carbon structure that enhances electrical conductivity in the z-direction are carbon micro-coils.

[0102] In a nineteenth exemplary embodiment, the method includes the steps of (a) placing at least first and second electrode assemblies on the subject's body, the first and second electrode assemblies including at least one electrode element having a skin-facing surface, each of the first and second electrode assemblies including at least one electrode element having a skin-facing surface, an anisotropic material layer having an outward-facing surface opposite the skin-facing surface, a first non-hydrogel conductive adhesive layer located between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer, and a skin contact layer including a biocompatible conductive adhesive and disposed on the skin-facing surface of the anisotropic material layer, and (b) applying an alternating voltage between the first and second electrode assemblies to generate an electric field. In this exemplary embodiment, the first non-hydrogel conductive adhesive layer facilitates electrical contact between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer. In some embodiments, the skin contact layer is disposed on the skin-facing surface of the anisotropic material layer.

[0103] In a twentieth exemplary embodiment of the method of the nineteenth exemplary embodiment, the first non-hydrogel conductive adhesive layer includes a material that enhances electrical conductivity in the z-direction perpendicular to the plane of the anisotropic material layer.

[0104] In a twenty-first exemplary embodiment of the method of the twentieth exemplary embodiment, the material that enhances electrical conductivity in the z-direction includes conductive particles having a three-dimensional carbon structure.

[0105] In a twenty-second exemplary embodiment of the method of the twenty-first exemplary embodiment, the conductive particles having a three-dimensional carbon structure are carbon microcoils.

[0106] In a twenty-third exemplary embodiment of the method of the nineteenth exemplary embodiment, a skin-facing surface of at least one electrode of the first electrode assembly is in electrical contact with a skin-contact layer of the first electrode assembly.

[0107] In a twenty-fourth exemplary embodiment of the method of the twenty-third exemplary embodiment, a skin-facing surface of at least one electrode of the second electrode assembly is in electrical contact with a skin-contact layer of the second electrode assembly.

[0108] In a twenty-fifth exemplary embodiment of the method of the nineteenth exemplary embodiment, the first or second electrode assembly includes an anisotropic material layer having a skin-facing surface and an opposite outward-facing surface, at least one electrode element of the electrode assembly is in electrical contact with the outward-facing surface of the anisotropic material layer of the electrode assembly, and a skin contact layer of the first electrode assembly is disposed on the skin-facing surface of the anisotropic material layer of the electrode assembly.

[0109] In a twenty-sixth exemplary embodiment, in a device or electrode assembly of any of the above exemplary embodiments, the conductive particles include a plurality of groups of conductive particles, and at least a portion of the conductive particles in some or all of the groups of conductive particles are aligned to define a conductive path through a thickness of the non-hydrogel conductive adhesive.

[0110] In a twenty-seventh exemplary embodiment, in the device of any one of the sixth to ninth exemplary embodiments, the polymer binder may be an acrylic binder.

[0111] In a twenty-eighth exemplary embodiment, the method includes the steps of: (a) positioning at least first and second electrode assemblies on the subject's body, the first and second electrode assemblies including at least one electrode element having a skin-facing surface, each of the first and second electrode assemblies including at least one electrode element having a skin-facing surface and at least one non-hydrogel conductive adhesive layer located on the skin-facing side of the at least one electrode element and in electrical contact with the skin-facing surface of the at least one electrode element, the at least one non-hydrogel conductive adhesive layer including one or more dielectric polymers and conductive particles having a three-dimensional carbon structure to enhance electrical conductivity in a Z direction perpendicular to the plane of the non-hydrogel conductive adhesive layer; and (b) applying an alternating voltage between the first electrode assembly and the second electrode assembly to generate an electric field.

[0112] In a twenty-ninth exemplary embodiment of the method of the twenty-eighth exemplary embodiment, the conductive particles having a three-dimensional carbon structure are carbon microcoils.

[0113] In a thirteenth exemplary embodiment, the non-hydrogel conductive adhesive can include one or more dielectric polymers and conductive particles having a three-dimensional carbon structure to enhance electrical conductivity in the z-direction perpendicular to the plane of the non-hydrogel conductive adhesive layer.

[0114] In a thirty-first exemplary embodiment of the non-hydrogel conductive adhesive of the thirtieth exemplary embodiment, the three-dimensional carbon structures for enhancing electrical conductivity in the z-direction are carbon microcoils.

[0115] In a thirty-second exemplary embodiment of the apparatus of the sixth exemplary embodiment, the material that promotes electrical conductivity in the z-direction perpendicular to the plane of the anisotropic material layer is a capacitive material.

[0116] A thirty-third exemplary embodiment includes an electrode assembly including: (a) at least one electrode element having a skin-facing surface; and (b) at least one non-hydrogel conductive adhesive layer located on a skin-facing side of the at least one electrode element and in electrical contact with the skin-facing surface of the at least one electrode element. In this exemplary embodiment, the at least one non-hydrogel conductive adhesive layer includes one or more of a dielectric polymer, a conductive particle, and a capacitive material to enhance electrical conductivity in a z-direction perpendicular to the plane of the non-hydrogel conductive adhesive layer.

[0117] In a thirty-fourth exemplary embodiment of the third exemplary embodiment device, either or both of the first non-hydrogel conductive adhesive layer or the skin contact layer further includes a scrim or mesh layer having a non-hydrogel conductive adhesive material on one or both sides of the scrim or mesh layer.

[0118] The features and advantages of the present disclosure are apparent from the detailed description, and the claims encompass all such features and advantages. Many variations will occur to those skilled in the art, and any variations equivalent to those described in the present disclosure are within the scope of the present disclosure. Those skilled in the art will appreciate that the concepts underlying the present disclosure can be used as a basis for designing other methods and systems to achieve some of the objectives of the present disclosure. Therefore, the claims are not to be considered as limited by the descriptions or examples.

Claims

1. 1. An apparatus comprising: at least one electrode element having a skin-facing surface; an anisotropic material layer having an outward-facing surface opposite the skin-facing surface; a first non-hydrogel conductive adhesive layer positioned between the skin-facing surface of the at least one electrode element and the outward-facing surface of the anisotropic material layer; a skin contact layer comprising a biocompatible conductive material and disposed on the skin-facing side of the anisotropic material layer; The device, wherein the first non-hydrogel conductive adhesive layer facilitates electrical contact between a skin-facing surface of the at least one electrode element and an outward-facing surface of the anisotropic material layer.

2. The device of claim 1 , wherein the biocompatible conductive material of the skin contact layer comprises a hydrogel.

3. The device of claim 1 , wherein the biocompatible conductive material of the skin contact layer is a non-hydrogel conductive adhesive.

4. 4. The device of claim 3, wherein the non-hydrogel conductive adhesive of the skin contact layer is different from the non-hydrogel conductive adhesive of the first non-hydrogel conductive adhesive layer.

5. The device described in claim 1, wherein the biocompatible conductive material of the skin contact layer includes a conductive composite material.

6. The device described in claim 5, wherein the conductive composite material includes an acrylic-based polymer or a silicone-based polymer, or a combination thereof.

7. 10. The device of claim 1, wherein the first non-hydrogel conductive adhesive layer comprises a material that promotes electrical conductivity in a z-direction perpendicular to the plane of the anisotropic material layer.

8. The first non-hydrogel conductive adhesive layer comprises: a dielectric material; and conductive particles dispersed within the dielectric material.

9. 10. The device of claim 8, wherein the conductive particles comprise carbon flakes, carbon particles, carbon nanotubes, single-walled carbon nanotubes, multi-walled carbon nanotubes, carbon black powder, graphite powder, carbon nanowires, carbon microcoils, or any combination thereof.

10. 8. The device of claim 7, wherein the material that promotes electrical conductivity in a z-direction perpendicular to the plane of the anisotropic material layer is a conductive material having a three-dimensional carbon structure.

11. The device of claim 10 , wherein the material that promotes electrical conductivity in the z-direction is a carbon microcoil.

12. 4. The device of claim 3, wherein either or both of the first non-hydrogel conductive adhesive layer and the skin contact layer further comprises a scrim or mesh layer having a non-hydrogel conductive adhesive material or a biocompatible conductive material on one or both sides of the scrim or mesh layer.

13. The anisotropic material layer comprises: i) a first thermal conductivity in a direction perpendicular to the plane of the anisotropic material layer, wherein the thermal conductivity of the anisotropic material layer in a direction parallel to the plane of the anisotropic material layer is at least two times higher than the first thermal conductivity; or ii) a first resistance in a direction perpendicular to the plane of the anisotropic material layer, wherein the resistance of the anisotropic material layer in a direction parallel to the plane of the anisotropic material layer is less than half of the first resistance, or iii) The apparatus of claim 1 having a combination of i) and ii).

14. The device described in claim 1, wherein the anisotropic material layer is a synthetic graphite sheet.

15. The device of claim 8 , wherein the dielectric material is a polymer binder.

16. The device of claim 1 , wherein the skin-contacting layer is disposed on the skin-facing surface of the anisotropic material layer.

17. 1. An electrode assembly comprising: at least one electrode element having a skin-facing surface; at least one non-hydrogel conductive adhesive layer located on a skin-facing side of the at least one electrode element and in electrical contact with the skin-facing surface of the at least one electrode element; The at least one non-hydrogel conductive adhesive layer comprises: one or more dielectric polymers; and conductive particles having a three-dimensional carbon structure for enhancing conductivity in the z-direction perpendicular to the plane of the non-hydrogel conductive adhesive layer.

18. 18. The electrode assembly of claim 17, wherein the conductive particles having a three-dimensional carbon structure that enhances conductivity in the z direction are carbon microcoils.

Images