Electrode assembly for applying tumor treating fields (ttfields) that include a sheet of graphite

Abstract

An alternating current electric field (e.g., TTField) can be applied to an individual body using one or more electrode assemblies, comprising a graphite plate, at least one conductive material layer disposed on the front side of the graphite plate, and an electrode element positioned behind the graphite plate. The electrode element has a front side disposed in electrical contact with the back side of the graphite plate. The graphite plate diffuses both heat and current in a direction parallel to the front side of the plate, which eliminates or at least minimizes hot spots on the electrode assembly. This, in turn, makes it possible to increase the current without exceeding a safe temperature limit (e.g., 41°C).

Description

[Technical Field]

[0001] Cross-reference to related applications

[0002] This application claims the benefits of U.S. Provisional Applications 63 / 230,438 (filed August 6, 2021), 63 / 275,841 (filed November 4, 2021) and 63 / 275,843 (filed November 4, 2021), each of which is incorporated herein by reference in its entirety. [Previous Technology]

[0003] Tumor Therapeutic Electric Field (TTField) therapy is a proven method for treating tumors using an alternating current electric field with a frequency between 50 kHz and 1 MHz (such as 100 kHz to 500 kHz). The alternating current electric field is induced by an array of electrodes (e.g., an array of capacitively coupled electrodes, also known as a transducer array) placed on opposite sides of an individual's body. When an AC voltage is applied between the opposite electrode arrays, an AC current flows through the electrode arrays and is coupled into the individual's body. Higher current is closely associated with higher therapeutic efficacy.

[0004] Figure 1A is a schematic representation of a prior art electrode assembly 40 including nine prior art electrode elements labeled X1 to X9. Figure 1B is a schematic cross-sectional view of electrode elements X7 to X9 of the electrode assembly 40 taken along the dashed line in Figure 1A.

[0005] As shown in Figure 1B, electrode element X7 (considered as an example) includes a metal layer (shown with diagonal outlines) and a ceramic (dielectric) layer. Individual conductive hydrogel layers are provided between each ceramic layer and the individual'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 opposite electrode assembly to generate a TTField in the individual's body.

[0006] During use, the hydrogel and skin beneath the electrode elements become hot, and for safety reasons, the skin temperature needs to be kept below the safety threshold (e.g., 41°C). This is because most of the heat occurs directly beneath the electrode elements X1 to X9 (as shown in Figure 1C). Prior art electrode assemblies have hot spots directly beneath the electrode elements and cooler areas located between the electrode elements. Furthermore, these hot spots limit the amount of current that can be transferred through the prior art electrode assemblies. [Summary of the Invention]

[0007] One aspect of the present invention relates to a first device for applying an alternating electric field to an individual body. The first device comprises: a graphite plate having a front side and a back side; at least one conductive material layer disposed on the front side of the plate, the at least one conductive material layer having a biocompatible front surface; and a first electrode element positioned behind the plate. The first electrode element has a first front side disposed to make electrical contact with the back side of the plate.

[0008] In some specific embodiments of the first device, the first electrode element includes (i) a first dielectric material layer having a front side and a back side and (ii) a first metal layer disposed on the back side of the first dielectric material layer. In these specific embodiments, the front side of the first dielectric material layer is the first front side of the first electrode element. These specific embodiments further include a first conductive material back layer positioned between the first front side of the first electrode element and the back side of the plate. The first conductive material back layer facilitates electrical contact between the first front side of the first electrode element and the back side of the plate.

[0009] Some specific examples of the first device further include a second electrode element positioned behind the board. The second electrode element has a second front side disposed for electrical contact with the back side of the board. In these specific examples, the second electrode element includes (i) a second dielectric material layer having a front side and a back side and (ii) a second metal layer disposed on the back side of the second dielectric material layer. The front side of the second dielectric material layer is the second front side of the second electrode element. A first conductive material back layer is positioned between the second front side of the second electrode element and the back side of the board. And the first conductive material back layer facilitates electrical contact between the second front side of the second electrode element and the back side of the board.

[0010] Some specific examples of the first device further include a second electrode element positioned behind the board. The second electrode element has a second front side disposed for electrical contact with the back side of the board. The second electrode element includes (i) a second dielectric material layer having a front side and a back side and (ii) a second metal layer disposed on the back side of the second dielectric material layer. The front side of the second dielectric material layer is the second front side of the second electrode element. In these specific examples, the device further includes a second conductive material back layer positioned between the second front side of the second electrode element and the back side of the board. The second conductive material back layer facilitates electrical contact between the second front side of the second electrode element and the back side of the board.

[0011] In some specific embodiments of the first device, the back layer of the first conductive material comprises a conductive hydrogel. In some specific embodiments of the first device, the back layer of the first conductive material comprises a conductive adhesive. In some specific embodiments of the first device, the back layer of the first conductive material comprises a conductive adhesive comprising an adhesive polymer and carbon powder, carbon particles, carbon fibers, carbon sheets, or carbon nanotubes. In some specific embodiments of the first device, the back layer of the first conductive material comprises a conductive adhesive with a thickness between 10 μm and 2,000 μm.

[0012] In some specific embodiments of the first device, the first electrode element includes a metal block having a front side, and the front side of the metal block is the first front side of the first electrode element.

[0013] In some specific embodiments of the first device, the first electrode element includes a metal block having a front side, and the front side of the metal block is the first front side of the first electrode element. These specific embodiments further include a first conductive material back layer positioned between the first front side of the first electrode element and the back side of the plate. The first conductive material back layer facilitates electrical contact between the first front side of the first electrode element and the back side of the plate.

[0014] In some specific embodiments of the first device, the first electrode element includes a metal block having a front side, and the front side of the metal block is the first front side of the first electrode element. In these specific embodiments, the first front side of the first electrode element is positioned to directly contact the back side of the plate.

[0015] In some specific embodiments of the first apparatus, the graphite plate is a pyrolytic graphite plate. In some specific embodiments of the first apparatus, the graphite plate is a graphite foil or graphitized polymer film made from compressed high-purity exfoliated mineral graphite.

[0016] In some specific embodiments of the first device, at least one conductive material layer comprises a hydrogel. In some specific embodiments of the first device, at least one conductive material layer comprises a hydrogel layer with a thickness between 50 μm and 2000 μm. In some specific embodiments of the first device, at least one conductive material layer comprises a conductive adhesive. In some specific embodiments of the first device, the first biocompatible conductive material back layer comprises a conductive adhesive, and the conductive adhesive comprises an adhesive polymer and carbon powder, carbon particles, carbon fibers, carbon sheets, or carbon nanotubes. In some specific embodiments of the first device, the first biocompatible conductive material back layer comprises a conductive adhesive with a thickness between 10 μm and 2000 μm.

[0017] Some specific examples of the first device further include a flexible self-adhesive substrate configured to support the plate, the first electrode element, and at least one conductive material layer such that the front surface of the at least one conductive material layer can be positioned against the skin of an individual. Some specific examples of the first device further include wires electrically connected to the first electrode element.

[0018] Another aspect of the present invention relates to a first method for applying an alternating electric field to a target region in an individual's body. The first method includes positioning a first electrode assembly at a first location on or in the individual's body. The first electrode assembly includes a first graphite plate having a first front side and a first back side, and the first electrode assembly is positioned such that the first front side of the first plate faces the target region. The first method also includes positioning a second electrode assembly at a second location on or in the individual's body. The second electrode assembly includes a second graphite plate having a second front side and a second back side, and the second electrode assembly is positioned such that the second front side of the second plate faces the target region. The first method also includes applying an alternating voltage between the first electrode assembly and the second electrode assembly. The application is performed after positioning the first electrode assembly and the second electrode assembly.

[0019] In some cases of the first method, the application is carried out by applying an alternating voltage between: (i) a first electrode element disposed in electrical contact with a first back surface and (ii) a second electrode element disposed in electrical contact with a second back surface. Where necessary, these cases may further include: measuring a first temperature of the first electrode element; measuring a second temperature of the second electrode element; and controlling the application based on the first and second temperatures.

[0020] In some cases of the first method, the first electrode assembly further includes a first conductive adhesive layer disposed on a first front side, and the second electrode assembly further includes a second conductive adhesive layer disposed on a second front side.

[0021] In some cases of the first method, each of the first and second graphite plates is a pyrolytic graphite plate. In some cases of the first method, each of the first and second graphite plates is a graphite foil or a graphitized polymer film made from compressed high-purity exfoliated mineral graphite.

Implementation Method

[0041] This application describes an exemplary combination of electrodes that can be used, for example, to deliver a TTField to an individual body and to treat one or more cancers or tumors located in an individual body.

[0042] When a TTField is applied to an individual's body, the temperature of the individual's body can increase proportionally with the increase of the induced electric field. The amount of current that can be driven by the transducer array is adjusted to keep the measured temperature at a location on the individual's body below a temperature threshold. As practiced in this technique, by reducing the operating current driven by the transducer array and reducing the intensity of the resulting TTField, the temperature at the location of the transducer array on the individual's body is controlled to be below the temperature threshold. This, in turn, becomes the most important limitation on the intensity of the TTField that can be used to treat tumors. Therefore, in this technique, it is necessary to safely apply the TTField intensity without exceeding the individual's skin temperature threshold.

[0043] For a transducer array containing multiple electrode elements, the portion of the transducer array located directly below the electrode elements becomes hotter than the portion located between the electrode elements. Furthermore, for a transducer array containing multiple electrode elements, a higher current flows through the electrode elements located along the array edges compared to electrode elements located towards the center of the array. Additionally, electrode elements located at corners or similar sharp turns within the array edges will have a higher current than other electrode elements near the edges and center of the array. This tendency of the transducer array to drive a higher current through electrode elements located along the array edges, especially at corners, is referred to herein as the "edge effect."

[0044] Non-uniform distribution of current through the transducer array due to the distribution or edge effects of the electrode elements can lead to higher temperature regions (or "hot spots"), for example, at the corners or edges of the transducer array. These hot spots are the first to reach the critical temperature limit, thus controlling the current reduction requirement. Therefore, the generation of hot spots can be limited by the maximum operating current driven by the transducer array and the strength of the resulting TTField.

[0045] The inventors have now recognized the need to reduce or minimize the uneven distribution of current, thereby allowing for the application of higher operating currents in transducer arrays. Transducer arrays operating with increased current can induce stronger TTFields in an individual body, ultimately resulting in better therapeutic outcomes. The electrode assembly disclosed herein allows current and heat to be evenly distributed above the array, thereby minimizing or eliminating hot spots.

[0046] The specific example described herein incorporates a graphite plate into the electrode assembly, as described below. This reduces the temperature of hot spots and increases the temperature of cooler areas when a given AC voltage is applied to the electrode assembly (compared to the prior art configuration described above). Therefore, the current can be increased (thereby enhancing therapeutic efficacy) without exceeding the safe temperature limit at any location on the individual's skin.

[0047] In some preferred embodiments, the graphite plate is a pyrolytic graphite plate. Notably, because graphite is nonmetallic, it advantageously prevents the transfer of ions into the individual body.

[0048] The invention will be more readily understood by referring to the following detailed description, examples, drawings, and claims, as well as the preceding and following descriptions. However, it should be understood that, unless otherwise specified, the invention is not limited to the specific devices, apparatuses, systems, and / or methods disclosed, and variations are naturally possible.

[0049] The headings are provided for convenience only and should not be construed as limiting the invention in any way. Specific examples described under any heading or in any part of the invention may be combined with specific examples described under the same or any other heading or in other parts of the invention.

[0050] Unless otherwise indicated herein or otherwise obviously contradicted by the context, the present invention covers any combination of the elements described herein and all possible variations thereof.

[0051] As used in the specification and the accompanying claims, unless the context clearly requires otherwise, the singular forms “a” and “the” include the plural references.

[0052] Figure 2 is a schematic representation of an electrode assembly 50 including electrode elements for applying a TTField to an individual's body, according to a specific example. In Figure 2, only two electrode elements, labeled E1 and E2, are shown, but additional electrode elements may be included in the electrode assembly 50. In an alternative specific example, the electrode assembly 50 includes only a single electrode element. It is worth noting that Figure 2 generally depicts the electrode assembly 50, and those electrode assemblies E1 and E2 may have different configurations (e.g., as described below in conjunction with Figures 3A to 8).

[0053] Figure 3A is a cross-sectional view of a first specific example of an electrode assembly 50a including electrode elements E1 and E2, taken along the dashed line in Figure 2.

[0054] In a specific example of FIG. 3A, electrode assembly 50a includes a pyrolytic graphite plate 70 having a front side (facing the individual's skin in FIG. 3A) and a back side. Examples of suitable forms of graphite include synthetic graphite, such as pyrolytic graphite (including but not limited to pyrolytic graphite plates (PGS) available from Panasonic Corporation, Kadoma City, 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 graphite foil supplied from MinGraph® 2010A flexible graphite available from Mineral Seal, Tucson, Arizona, USA), or graphitized polymer films, such as graphitized polyimide films (including but not limited to graphitized polyimide films supplied from Kaneka Chemical Co., Ltd., Sanaoka City, Tochigi Prefecture, Japan).

[0055] The electrode assembly 50a further includes at least one conductive material layer 60 disposed on the front side of the plate 70, and the at least one conductive material layer 60 has a biocompatible front surface. It should be noted that in the specific example illustrated in FIG3, only a single conductive material layer 60 exists, and this single layer is biocompatible. However, in alternative specific examples (not shown in the figures), more than one layer may exist, in which case only the front layer must be biocompatible. At least one material layer 60 is configured to ensure good electrical contact between the device and the body. In some specific examples, at least one material layer 60 should cover the entire front side of the pyrolytic graphite plate 70. The size of at least one material layer 60 may be equal to or larger than the pyrolytic graphite plate 70. In some specific examples (and illustrated in FIG3A), at least one conductive material layer 60 comprises a single hydrogel layer. In these specific examples, the thickness of the hydrogel can be between 50 μm and 2000 μm, such as 100 μm to 1000 μm or even 300 μm to 500 μm. In some specific examples, at least one conductive material layer 60 is a single non-hydrogel biocompatible conductive adhesive layer, such as FLX068983-FLEXcon® OMNI-WAVE TMTT 200 Black H-502 150 Polymer H-9 44PP-8 developed by FLEXcon in Spencer, Massachusetts, USA, or other such omnidirectional wave (OMNI-WAVE) products from FLEXcon; or ARcare® 8006 conductive adhesive composition manufactured and marketed by Adhesive Research, Inc. (Glenrock, Pennsylvania, USA). The non-hydrogel conductive adhesive may comprise anhydrous polymers with adhesive properties and carbon particles, toners, carbon fibers, carbon sheets, or carbon nanotubes. The adhesive polymer may be, for example, an acrylic polymer or a polysiloxane polymer or a combination thereof, which can be used as an acrylic or polysiloxane-based carbon-filled adhesive tape. The adhesive may further comprise one or more conductive polymers (such as polyaniline (PANI) or poly(3,4-ethylenedioxythiophene) (PEDOT) or other conductive polymers known in the art). The conductive filler in at least one conductive material layer 60 shall be non-metallic. In such specific examples, the thickness of the biocompatible conductive adhesive may be between 10 μm and 2,000 μm, such as 20 μm to 1,000 μm or even 30 μm to 400 μm.

[0056] The electrode assembly 50a further includes a first electrode element E1 positioned behind the plate 70. The first electrode element E1 has a first front side disposed to make electrical contact with the back side of the plate 70. In a specific example of FIG. 3A, the first electrode element E1 includes a first dielectric material (e.g., ceramic) layer 310 having a front side and a back side, and a first metal layer 320 disposed on the back side of the first dielectric material layer 310. The front side of the first dielectric material layer 310 is the first front side of the first electrode element E1. It should be noted that although the dielectric material 310 is depicted as "ceramic" in the figures (e.g., FIG. 3A), a variety of other suitable dielectric materials may be used instead of ceramic materials. Examples include a polymer layer with a dielectric constant of at least 10, or another material with a dielectric constant of at least 10.

[0057] In some specific examples, the dielectric constant of the dielectric material layer 310 may be in the range of 10 to 50,000. In some specific examples, the dielectric material layer 310 comprises a high-dielectric polymer 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 specific examples are particularly advantageous because the dielectric constant of such materials is about 40. In some specific examples, the polymer layer may be poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene-chlorofluoroethylene) or "poly(VDF-TrFE-CTFE-CFE)".

[0058] In some specific examples, the dielectric layer 310 comprises a terpolymer containing monomer polymer units in any suitable molar ratio, such as VDF, TrFE, CFE, and / or CTFE. Suitable terpolymers include, for example, terpolymers having 30 to 80 molar % VDF, 5 to 60 molar % TrFE, wherein CFE and / or CTFE constitute the molar % balance of the terpolymer.

[0059] In some specific embodiments, plate 70 has a center of mass, and the distance from the center of mass of the first front side of the first electrode element E1 to the center of mass of plate 70 is less than 3 cm. In some specific embodiments, plate 70 has a center of mass and a dimension (e.g., length or width) parallel to the back side of plate 70, and the distance from the center of mass of the first front side of the first electrode element E1 to the center of mass of plate 70 is less than 30% or less than 10% of the dimension.

[0060] The electrode assembly 50a further includes a first conductive material back layer 80 positioned between the first front side of the first electrode element E1 (i.e., the front side of the first dielectric material layer 310) and the back side of the plate 70. The first conductive material back layer 80 facilitates electrical contact between the first front side of the first electrode element E1 and the back side of the plate 70. In some specific examples, the conductive material back layer 80 is a hydrogel layer. However, in alternative specific examples, different conductive materials (e.g., conductive grease, conductive adhesive, conductive tape, conductive composite, etc.) may be used. In some specific examples, the conductive material 80 may be a non-hydrogel conductive adhesive, as described above.

[0061] Electrode assembly 50a may include one or more additional electrode elements as needed. In a specific example described, electrode assembly 50a includes a second electrode element E2 positioned behind plate 70. The second electrode element E2 has a second front side disposed to make electrical contact with the back side of plate 70. The two electrode elements E1 and E2 in FIG. 3A have the same structure. Therefore, the second electrode element E2 includes a second dielectric material (e.g., ceramic) layer 310 having a front side and a back side, and a second metal layer 320 disposed on the back side of the second dielectric material layer 310. The front side of the second dielectric material layer 310 is the second front side of the second electrode element E2. In some specific examples, the total area of ​​all electrode elements is less than the area of ​​plate 70, less than half the area of ​​plate 70, less than one-quarter the area of ​​plate 70, or less than one-tenth the area of ​​plate 70.

[0062] A first conductive material back layer 80 is positioned between the second front side of the second electrode element E2 (i.e., the front side of the second dielectric material layer 310) and the back side of the plate 70. The first conductive material back layer 80 facilitates electrical contact between the second front side of the second electrode element E2 and the back side of the plate 70. As described with respect to E1 and shown in FIG. 3A, the conductive material 80 may be a hydrogel layer, but in alternative specific embodiments, different conductive materials may be used (e.g., conductive grease, conductive adhesives including the non-hydrogel conductive adhesives described above, conductive tapes, conductive composites, etc.).

[0063] The metal layers 320 of all electrode elements (i.e., E1 and E2 in the specific examples described) can be connected together to the conductor 90 in a wired manner (e.g., using wires, traces on a flexible circuit, etc.). The conductor 90 supplies AC voltage from an AC voltage generator (not shown) to the electrode elements to generate a TTField for treatment when the electrode assembly 50a is attached to the individual's body.

[0064] As needed, the electrode assembly 50a includes a flexible self-adhesive substrate 55 configured to support a support plate 70, a first electrode element E1 (and any other electrode elements present in the electrode assembly) and at least one conductive material layer 60, such that at least one conductive material layer 60 can be positioned against the individual's skin.

[0065] As mentioned above, Figure 2 is a schematic planar representation of the electrode assembly 50 including electrode elements E1 and E2. This view in Figure 2 (not to scale) also shows that the area of ​​plate 70 is larger than the combined area of ​​electrode elements E1 and E2 (e.g., at least twice, at least four times, or at least ten times larger). When an AC voltage is applied to electrode elements E1 and E2, heat is diffused throughout plate 70, thus minimizing or eliminating hot spots.

[0066] This reduction in hot spots (compared to the prior art) becomes apparent by comparing Figures 1C and 3B. More specifically, Figure 1C illustrates the current distribution and heat generation of a prior art electrode element, each located on a conductive hydrogel layer covering approximately the same area as the electrode element. As shown in Figure 1C, all current passes through the hydrogel layer directly beneath the electrode element, thus creating a hot spot directly beneath the electrode element.

[0067] It might initially be thought that this problem could be solved by increasing the area of ​​the hydrogel to cover all areas between the electrode elements (i.e., by covering an area in the xy plane larger than the area of ​​the electrode elements). However, this is not the case. More specifically, Figure 1D shows the current distribution and heat generation of this hypothetical electrode assembly. As shown in Figure 1D, all currents pass through the hydrogel layer directly beneath the electrode elements, creating hot spots directly beneath the electrode elements.

[0068] In contrast, Figure 3B shows the current distribution of the specific example of Figure 3A. As shown in Figure 3B, the current is still distributed only in the conductive material back layer (e.g., 80 in Figure 3B) in the region below the electrode elements. However, the pyrolytic graphite plate 70 diffuses heat over its entire area due to its higher thermal conductivity in the horizontal direction. In addition to the diffusion of heat, the low resistance of plate 70 in the horizontal direction causes the current to diffuse outward throughout plate 70, and this further current distribution continues in the conductive material layer 60, and thus diffuses to the individual's skin. Because both the current and heat in this specific example diffuse over a larger area of ​​the conductive material layer 60, hot spots are eliminated (or at least minimized). This means that for a given applied AC voltage, the temperature of the hottest spot below the electrode assembly in the specific examples of Figures 3A / B will be lower than the temperature of the hottest spot below the electrode assembly in the prior art example of Figure 1. Therefore, the current can be increased (relative to the prior art current) without exceeding the safe temperature limit at any point below the electrode assembly in the specific example of Figure 3A. Furthermore, this increased current will significantly enhance the efficacy of TTField treatment. Similar results can be achieved by replacing the hydrogel with a conductive adhesive complex.

[0069] The superior performance of the specific example shown in Figure 3A is illustrated in Figures 4A, 4B, and 4C. Figure 4A is a thermal image of a prior art electrode assembly comprising two electrode elements and a hydrogel layer disposed on the front side of the electrode elements. There is no graphite plate between the front side of the electrode elements and the back side of the hydrogel layer. In use, the front side of the hydrogel layer is positioned on the individual's skin. Figure 4A shows the hot spots generated in the area corresponding to the electrode elements.

[0070] Figure 4B is a thermal image of the electrode assembly corresponding to the specific example of Figure 3A, wherein pyrolytic graphite 70 is positioned between the front side of electrode elements E1 and E2 and the back side of conductive layer 60, and conductive layer 60 is made of hydrogel. Figure 4B shows that hot spots such as those generated in prior art electrode assemblies have been minimized, and also shows that the maximum temperature has been reduced. Figure 4C is a graph comparing the thermal performance of the specific example of Figure 3A (with pyrolytic graphite) and the prior art (without graphite) for the same applied current (500 mA). It is worth noting that the hottest part of the prior art electrode assembly is 41°C. However, when the same 500 mA current is applied to the specific example of Figure 3A, the hottest part of the electrode assembly is only 32°C. Similar results were obtained by conducting a similar experiment using graphite foil made from compressed high-purity exfoliated mineral graphite.

[0071] In related experiments, the optimized conventional array (without graphite plates) operating at an applied current of 2 A operated at an average temperature of at most 40°C, and was therefore limited. An array of the same type with additional pyrolytic graphite plates (as illustrated in Figure 3A) was able to operate at an increased power level (using an applied current of 3 A) and at an average temperature of 38°C, 2 to 3°C below the temperature threshold. This result indicates that the apparatus and method of the present invention described herein should be able to achieve more beneficial therapeutic results by operating at a higher applied current.

[0072] Experimental simulations of electrodes used for treating target sites in vivo compared the heat distribution obtained using graphite plates with that obtained using metal plates. Halfway through the experiment, a prosthetic gel was sandwiched between two metal (aluminum) plates, and a voltage was applied between the two plates (directly to the center of the plates). In the other half of the experiment, the prosthetic gel was sandwiched between two pyrolytic graphite plates, and a voltage was applied between the two pyrolytic graphite plates (directly to the center of the plates). When a voltage was applied between a pair of metal (aluminum) plates, the higher current density at the edges of the plates caused uneven heating in different areas. In contrast, applying a voltage between the two graphite plates advantageously produced a much more uniform current density at the center and edges of the plates, resulting in a more uniform temperature distribution across the plates.

[0073] Figures 4D and 4E show thermal imaging images of a simulated electrode array constructed using a metal (aluminum) plate and a simulated electrode array constructed using a pyrolytic graphite plate, respectively. The aluminum plate produces a non-uniform heat distribution pattern, which causes the outer edges to reach the critical temperature first, thus controlling the current reduction requirement. In contrast, the pyrolytic graphite plate produces an extremely uniform heat distribution across the entire plate.

[0074] Figure 4F depicts the experimental results of applying the TTField to the rat trunk (using a smaller animal array) using electrode arrays with and without graphite plates. Two lower traces show the currents measured for two rats using the prior art electrode arrays depicted in Figures 1A / 1B, while two higher traces show the currents measured for two rats using the electrode elements depicted in Figure 3A (using graphite plates). The thermal setpoint was the same for all procedures. Notably, when the graphite plate is included, the improved heat and current distribution can be attributed to a 20% decrease in resistance and a 50% increase in current caused by graphite at the same thermal setpoint. And because the higher current is associated with improved results, these experiments demonstrate that incorporating a graphite layer into the electrode array can provide improved results.

[0075] FIG5 is a cross-sectional view of a second specific example of an electrode assembly 50b including electrode elements E1 and E2, taken along the dashed line in FIG2. The specific example of FIG5 is similar to the specific example of FIG3A in all respects (including the reference numerals), except as follows. The specific example of FIG3A includes a large conductive material back layer 80 (e.g., hydrogel) positioned between the plate 70 and the front faces of both the first electrode element E1 and the second electrode element E2. In contrast, the specific example of FIG5 includes separate regions of conductive material 380 for each individual electrode element. Therefore, the specific example of FIG5 includes a first conductive material back layer 380 positioned between the first front face of the first electrode element E1 and the back face of the plate 70, and also includes a second conductive material back layer 380 positioned between the second front face of the second electrode element E2 and the back face of the plate 70. The first and second conductive material back layers 380 facilitate electrical contact between the respective electrode front faces and the back face of the plate 70. In some specific examples, the conductive material back layer 380 is a hydrogel layer. However, in alternative specific examples, different conductive materials may be used (e.g., conductive grease, conductive adhesives including the non-hydrogel conductive adhesives discussed above, conductive tapes, conductive composites, etc.). In some specific examples, the total area of ​​all electrode elements is less than the area of ​​plate 70, less than half the area of ​​plate 70, less than one-quarter the area of ​​plate 70, or less than one-tenth the area of ​​plate 70.

[0076] As in the specific example of Figure 3A, the current in the specific example of Figure 5 is still concentrated in the conductive material back layer 380 only in the region below the electrode elements. The pyrolytic graphite plate 70 dissipates heat and current, eliminating or at least minimizing hot spots, as described above in conjunction with the specific example of Figure 3A. This means that for a given applied AC voltage, the temperature of the hottest spot below the electrode assembly in the specific example of Figure 5 will be lower than the hottest spot below the electrode assembly in the prior art example of Figure 1. Therefore, the current can be increased (relative to the prior art current) without exceeding the safe temperature limit at any point below the electrode assembly in the specific example of Figure 5. And this increase in current will advantageously enhance the efficacy of TTField therapy.

[0077] FIG6 is a cross-sectional view of a third specific example of an electrode assembly 50c including a single electrode element E1. The specific example of FIG6 is similar to the specific example of FIG3A, except that the specific example of FIG6 does not include a dielectric material layer. In the specific example of FIG6, the electrode assembly 50c includes a pyrolytic graphite plate 70 having a front side (facing the individual's skin in FIG6) and a back side. This plate 70 is similar to the plate 70 described above in conjunction with FIG3A.

[0078] The electrode assembly 50c further includes at least one conductive material layer 60 disposed on the front side of the plate 70, and the at least one conductive material layer 60 has a biocompatible front surface. It should be noted that in the specific example illustrated in FIG. 6, only a single conductive material layer 60 exists, and this single layer is biocompatible. However, in alternative specific examples (not shown in the figures), more than one layer may exist, in which case only the front layer must be biocompatible. The at least one conductive material layer 60 is configured to ensure good electrical contact between the device and the body. In a preferred specific example, the at least one conductive material layer 60 should cover the entire front side of the pyrolytic graphite plate 70. The size of the at least one conductive material layer 60 may be equal to or greater than (i.e., the coverage area is equal to or greater than) the pyrolytic graphite plate 70. In some specific examples, the at least one conductive material layer 60 comprises a single hydrogel layer. In these specific examples, the thickness of the hydrogel can be between 50 μm and 2000 μm, such as 100 μm to 1000 μm or even 300 μm to 500 μm. In some specific examples, at least one conductive material layer 60 is a single non-hydrogel biocompatible conductive adhesive layer as described above. In some specific examples, at least one conductive material layer 60 is a single non-hydrogel biocompatible conductive adhesive layer, such as the omnidirectional wave product from FLEXcon discussed above, or the ARcare® product from Adhesive Research Corporation. The non-hydrogel conductive adhesive layer may comprise an anhydrous polymer (e.g., an acrylic polymer or a polysiloxane polymer or a combination thereof) with adhesive properties and a conductive filler. The conductive filler in at least one conductive material layer 60 should be non-metallic. In these specific examples, the thickness of the biocompatible conductive adhesive can be between 10 μm and 2,000 μm, such as 20 μm to 1,000 μm or even 30 μm to 400 μm.

[0079] The electrode assembly 50c further includes a first electrode element E1 positioned behind the plate 70. The first electrode element E1 includes a metal block 500 having a front side disposed to make electrical contact with the back side of the plate 70. In the specific embodiment of FIG6, the front side of the metal block 500 is the first front side of the first electrode element E1. Therefore, the specific embodiment of FIG6 differs from the specific embodiments of FIG3A or FIG5 in that it does not contain a dielectric material layer. The positional relationship between the first electrode element E1 and the plate 70 in this specific embodiment of FIG6 can be described above in conjunction with FIG3A.

[0080] The electrode assembly 50c further includes a first conductive material back layer 80 positioned between the first front side of the first electrode element E1 (i.e., the front side of the metal block 500) and the back side of the plate 70. The first conductive material back layer 80 facilitates electrical contact between the first front side of the first electrode element E1 and the back side of the plate 70. In some specific embodiments, the conductive material back layer 80 is a hydrogel layer. However, in alternative specific embodiments, different conductive materials may be used (e.g., conductive grease, conductive adhesives including the non-hydrogel conductive adhesives described above, conductive tapes, conductive composites, etc.).

[0081] The metal block 500 of the electrode element E1 is connected to the wire 90 in a wire manner (e.g., using a wire, a trace on a flexible circuit, etc.), which supplies AC voltage from an AC voltage generator (not shown) to the electrode element to generate a TTField for treatment when the electrode assembly 50c is attached to the individual body.

[0082] The electrode assembly 50c may include one or more additional electrode elements (not shown) as needed, which have the same structure as the electrode element E1 and are positioned to have the same function. In this case, the metal blocks 500 of all electrode elements can be connected together to the conductor 90 in a wired manner (e.g., using wires, traces on flexible circuits, etc.).

[0083] In some specific instances that include only a single electrode element E1, the area of ​​plate 70 is larger than the area of ​​electrode element E1 (e.g., at least twice, at least four times, or at least ten times larger). In some specific instances that include multiple electrode elements (not shown), the area of ​​plate 70 is larger than the total area of ​​all electrode elements (e.g., at least twice, four times, or ten times larger). When an AC voltage is applied to the electrode element, heat is diffused across the entire plate 70, thus minimizing or eliminating hot spots.

[0084] Similar to the specific example in Figure 3A, the pyrolytic graphite plate 70 in the specific example in Figure 6 diffuses heat and current, as described above in conjunction with the specific example in Figure 3A, thus eliminating or at least minimizing hot spots. This means that for a given applied AC voltage, the temperature of the hottest spot below the electrode assembly in the specific example in Figure 6 will be lower than the hottest spot below the electrode assembly in the prior art example in Figure 1. Therefore, the current can be increased (relative to the prior art current) without exceeding the safe temperature limit at any point below the electrode assembly in the specific example in Figure 6. Furthermore, this increase in current will advantageously enhance the efficacy of TTField treatment.

[0085] FIG7 is a cross-sectional view of a fourth specific example of an electrode assembly 50d including a single electrode element E1. The specific example of FIG7 is similar to the specific example of FIG6, except that the first front side of the first electrode element E1 (i.e., the front side of the metal block 600) is positioned to directly contact the back side of the plate 70 (instead of being electrically connected via a conductive material intermediate layer).

[0086] Similar to the specific example in Figure 6, the pyrolytic graphite plate 70 in the specific example in Figure 7 diffuses heat and current, as described above in conjunction with the specific example in Figure 3A, thus eliminating or at least minimizing hot spots. This means that for a given applied AC voltage, the temperature of the hottest spot below the electrode assembly in the specific example in Figure 7 will be lower than the hottest spot below the electrode assembly in the prior art example in Figure 1. Therefore, the current can be increased (relative to the prior art current) without exceeding the safe temperature limit at any point below the electrode assembly in the specific example in Figure 7. Furthermore, this increase in current will advantageously enhance the efficacy of TTField treatment.

[0087] Figure 8 is a cross-sectional view of a fifth specific example of an electrode assembly 50e including a single electrode element E1. The specific example of Figure 8 is similar to the specific example of Figure 7, except that a capacitor 700 is added in series with and behind the metal block 600. A similar addition of a capacitor 700 in series with and behind the metal block 600 is also conceivable for the specific example of Figure 6.

[0088] Figure 9 illustrates how a pair of electrode assemblies 50a of Figure 3A can be used to apply an alternating electric field to a target area in an individual's body. The individual may be a human or another mammal, including but not limited to rats and mice. (It should be noted that any of the electrode assemblies described above in conjunction with Figures 5 through 8 may be used instead of the electrode assembly 50a of Figure 3A shown herein.)

[0089] The method includes positioning a first electrode assembly 50a at a first location on or in the body of an individual. (In the example depicted in FIG9, the first electrode assembly 50a is positioned on the skin of the individual on the right side of the head, facing a target region, such as a tumor.) The first electrode assembly 50a may be constructed as previously described herein. In the specific example of FIG9, the first electrode assembly 50a includes a first pyrolytic graphite plate 70 having a first front side and a first back side. During use, the first electrode assembly 50a is positioned such that the first front side of the first plate 70 faces the target region.

[0090] The method also includes positioning the second electrode assembly 50a at a second location on or in the body of an individual. (In the example depicted in FIG9, the second electrode assembly 50a is positioned on the skin of the individual on the left side of the head, facing the target region.) The second electrode assembly 50a may be constructed as previously described herein. In the specific example of FIG9, the second electrode assembly 50a includes a second pyrolytic graphite plate 70 having a second front side and a second back side. During use, the second electrode assembly 50a is positioned such that the second front side of the second plate 70 faces the target region.

[0091] The method further includes applying an alternating current voltage 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 positioned. The application can be carried out by applying an alternating current voltage between (i) a first electrode element positioned to make electrical contact with a first back surface of the first plate 70 and (ii) a second electrode element positioned to make electrical contact with a second back surface of the second plate 70.

[0092] In some specific examples, the first electrode assembly 50a further includes a first biocompatible conductive material layer 60 disposed on a first front side of the first plate 70. Correspondingly, the second electrode assembly further includes a second biocompatible conductive material layer 60 disposed on a second front side of the second plate 70. As described above, the biocompatible conductive material 60 may be a hydrogel or a conductive grease, including conductive adhesives such as the non-hydrogel conductive adhesives discussed above, conductive strips, conductive composites, etc.

[0093] In some specific embodiments, the first electrode assembly 50a further includes a first conductive material back layer 80 (as described above), which is positioned between a first front side of the first electrode element of the first electrode assembly 50a and a first back side of the first plate 70. Correspondingly, the second electrode assembly further includes a second conductive material back layer 80 (as described above), which is positioned between a second front side of the second electrode element of the second electrode assembly and a second back side of the second plate 70.

[0094] An AC voltage between the first electrode assembly and the second electrode assembly can be applied by an AC voltage generator 820. In some specific examples, 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 use temperature measurements to control the amplitude of the current to be delivered through the first and second electrode assemblies 50a in order to maintain the temperature below a safe threshold (e.g., 41°C). This can be achieved, 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 described below.

[0095] Figure 9 depicts an example of hardware suitable for this purpose. More specifically, a temperature sensor 800 (e.g., a thermistor) is positioned in thermal contact with the respective electrode elements 310 / 320 within each of the electrode assemblies 50a. The temperature sensor 800 (e.g., at the first and second electrode elements in the first and second electrode assemblies, respectively) measures a first temperature and a second temperature, and the controller 822 controls the output of the AC voltage generator 820 based on these temperatures.

[0096] Imagine similar specific examples and methods of using any one of the electrode combinations 50a to 50e or a combination thereof to replace any one or both of the first electrode combination 50a and the second electrode combination 50a.

[0097] In the specific examples discussed above in conjunction with Figures 2 to 9, plate 70 is made of pyrolytic graphite. However, in alternative specific examples, plate 70 may be made of other types of graphite, including but not limited to other synthetic graphite, such as graphite foil made of compressed high-purity exfoliated mineral graphite (including but not limited to MinGraph® 2010A flexible graphite available from Mineral Sealing, Tucson, Arizona, USA); isotropic graphite (including but not limited to isotropic graphite grade G330 available from East Sea Carbon (Europe), Oldbury, UK; or double-sided carbon ribbons for scanning electron microscopy available from Thermo Fisher Scientific, a subsidiary of Thermo Fisher Scientific, Hampton, New Hampshire, USA).

[0098] Although the invention has been disclosed with reference to certain specific examples, numerous modifications, alterations, and changes to the described specific examples are possible without departing from the field and scope of the invention as defined in the appended claims. Therefore, it is intended that the invention is not limited to the described specific examples, but has the full scope defined by the language of the following claims and their equivalents. [Simplified Explanation of the Diagram]

[0022] [Figure 1A] is a schematic representation of a prior art electrode assembly.

[0023] [Figure 1B] is a cross-sectional view of the electrode element of the prior art electrode assembly taken along the dashed line in Figure 1A.

[0024] [Figure 1C] is a cross-sectional view showing the heat generation characteristics of prior art electrode elements.

[0025] [Figure 1D] is a cross-sectional view showing the heat generation characteristics of a hypothetical modification of the electrode element in Figure 1B.

[0026] [Figure 2] is a planar schematic representation of an electrode assembly including electrode elements for applying TTField to an individual body.

[0027] [Figure 3A] is a cross-sectional view of the first specific example including electrode elements E1 and E2, taken along the dashed line in Figure 2.

[0028] [Figure 3B] is a cross-sectional view showing the heat generation characteristics of a specific example of Figure 3A.

[0029] [Figure 4A] is a thermal image of a prior art electrode assembly.

[0030] [Figure 4B] is a thermal image of the electrode assembly corresponding to the specific example in Figure 3A.

[0031] [Figure 4C] is a graph comparing the thermal characteristics of the prior art electrode assembly with the specific example in Figure 3A.

[0032] [Figure 4D] shows a thermal camera image of a simulated electrode array constructed using a metal (aluminum) plate.

[0033] [Figure 4E] shows a thermal camera image of a simulated electrode array constructed using pyrolytic graphite plates.

[0034] [Fig. 4F] depicts the experimental results when using an electrode array with or without graphite plates to apply the TTField to the rat trunk.

[0035] [Figure 5] is a cross-sectional view of the second specific example including electrode elements E1 and E2, taken along the dashed line in Figure 2.

[0036] [Figure 6] is a cross-sectional representation of a third specific example including a single electrode element E1.

[0037] [Figure 7] is a cross-sectional representation of a fourth specific example including a single electrode element E1.

[0038] [Figure 8] is a cross-sectional representation of a fifth specific example including a single electrode element E1.

[0039] [Figure 9] is a block diagram of a system incorporating a combination of two electrodes used to apply TTField to an individual's body.

[0040] Various specific examples are described in detail below with reference to the accompanying drawings, wherein the same symbol for the same element represents the same element.

Claims

1. A device for applying an alternating electric field to an individual body, the device comprising: a graphite plate having a front side and a back side; at least one conductive material layer disposed on the front side of the plate, wherein the at least one conductive material layer has a biocompatible front surface; and a first electrode element positioned behind the plate, the first electrode element having a first front side disposed to electrically contact the back side of the plate.

2. The device of claim 1, wherein the first electrode element comprises (i) a first dielectric material layer having a front side and a back side and (ii) a first metal layer disposed on the back side of the first dielectric material layer, wherein the front side of the first dielectric material layer is the first front side of the first electrode element, and wherein the device further comprises a first conductive material back layer positioned between the first front side of the first electrode element and the back side of the plate, and wherein the first conductive material back layer facilitates electrical contact between the first front side of the first electrode element and the back side of the plate.

3. The device of claim 2, further comprising a second electrode element positioned behind the plate, the second electrode element having a second front side disposed for electrical contact with the back side of the plate, wherein the second electrode element comprises (i) a second dielectric material layer having a front side and a back side and (ii) a second metal layer disposed on the back side of the second dielectric material layer, wherein the front side of the second dielectric material layer is the second front side of the second electrode element, and wherein the first conductive material back layer is positioned between the second front side of the second electrode element and the back side of the plate, and wherein the first conductive material back layer facilitates electrical contact between the second front side of the second electrode element and the back side of the plate.

4. The device of claim 2, further comprising a second electrode element positioned behind the plate, the second electrode element having a second front side disposed for electrical contact with the back side of the plate, wherein the second electrode element comprises (i) a second dielectric material layer having a front side and a back side and (ii) a second metal layer disposed on the back side of the second dielectric material layer, wherein the front side of the second dielectric material layer is the second front side of the second electrode element, and wherein the device further comprises a second conductive material back layer positioned between the second front side of the second electrode element and the back side of the plate, and wherein the second conductive material back layer facilitates electrical contact between the second front side of the second electrode element and the back side of the plate.

5. The device of claim 2, wherein the back layer of the first conductive material comprises a conductive hydrogel.

6. The device of claim 2, wherein the first conductive material back layer comprises a conductive adhesive.

7. The apparatus of claim 6, wherein the conductive adhesive comprises an adhesive polymer and carbon powder, carbon particles, carbon fibers, carbon sheets or carbon nanotubes.

8. The device of claim 1, wherein the first electrode element includes a metal block having a front side, and wherein the front side of the metal block is the first front side of the first electrode element.

9. The device of claim 8, further comprising a first conductive material back layer positioned between a first front side of the first electrode element and a back side of the plate, wherein the first conductive material back layer facilitates electrical contact between the first front side of the first electrode element and the back side of the plate.

10. The device of claim 8, wherein the first front side of the first electrode element is positioned in direct contact with the back side of the plate.

11. The apparatus of claim 1, wherein the graphite plate is a pyrolytic graphite plate.

12. The apparatus of claim 1, wherein the graphite plate is a graphite foil or graphitized polymer film made from compressed high-purity exfoliated mineral graphite.

13. The device of claim 1, wherein the at least one conductive material layer comprises a hydrogel.

14. The apparatus of claim 1, wherein the at least one conductive material layer comprises a conductive adhesive.

15. The apparatus of claim 14, wherein the conductive adhesive comprises an adhesive polymer and toner, carbon particles, carbon fibers, carbon sheets or carbon nanotubes.

16. The device of claim 1, further comprising a flexible self-adhesive substrate configured to support the plate, the first electrode element and the at least one conductive material layer, such that the front surface of the at least one conductive material layer can be positioned against the skin of an individual.

17. The device of claim 1, further comprising a wire electrically connected to the first electrode element.

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