Apparatuses for delivering tumor treating fields having electrode elements with nonuniform thicknesses and methods for manufacturing same

Abstract

A device for delivering a tumor therapeutic field to the body of a subject. The device includes: a plurality of electrically coupled electrode elements disposed on the body of a subject and capable of delivering a tumor therapeutic field to the body of the subject, wherein at least one of the plurality of electrically coupled electrode elements includes a dielectric layer having a first surface facing the body of the subject and a second surface opposite to the first surface, and at least one of the first surface and the second surface of the dielectric layer is a non-planar surface.

Description

Technical Field

[0001] This application relates to an apparatus and a method for manufacturing the same for delivering an electrode element with a non-uniform thickness to a tumor treatment field. Cross-referencing of related applications

[0002] This application claims priority to U.S. Patent Application No. 17 / 886,345, filed August 11, 2022, and U.S. Provisional Patent Application No. 63 / 232,241, filed August 12, 2021, which are incorporated herein by reference. Prior Technology

[0003] A Tumor Therapeutic Field (TTField) is a low-intensity (e.g., 1 to 4 V / cm) alternating electric field in the mid-frequency range (e.g., 50 kHz to 1 MHz, such as 50 to 500 kHz) that can be used to treat tumors as described in U.S. Patent No. 7,565,205. TTField therapy is an approved monotherapy for recurrent glioblastoma multiforme (GBM) and an approved combination therapy with chemotherapy for newly diagnosed GBM patients. TTField can also be used to treat tumors in other parts of the subject's body (e.g., the lungs, ovaries, pancreas). For example, TTField therapy is an approved combination therapy with chemotherapy for malignant pleural mesothelioma (MPM). TTField non-invasively senses the area of ​​interest by applying an AC voltage between sensors (e.g., an array of capacitively coupled electrode elements) placed directly on the patient's body (e.g., using the Novocure Optune™ system).

[0004] In the context of GBM (GBM), a conventional method for setting up the sensors is to place a first pair of sensors on the front and back of the head, and a second pair of sensors on the right and left sides of the head. In the context of treating mesothelioma, a conventional method for setting up the sensors is to place a first pair of sensors on the front and back of the torso, and a second pair of sensors on the right and left sides of the torso. An AC voltage generator applies an AC voltage (e.g., 200 kHz in the context of GBM, or 150 kHz in the context of mesothelioma) between the first pair of sensors for a first time interval (e.g., one second), which generates an electric field with field lines oriented generally in the front-back direction. Then, the AC voltage generator applies an AC voltage at the same frequency between the second pair of sensors for a second time interval (e.g., one second), which generates an electric field with field lines oriented generally in the left-right direction. The system then repeats this sequence of two steps during the duration of the treatment. Summary of the Invention

[0005] The present invention provides a device for delivering a tumor therapeutic field to a subject's body, the device comprising: a plurality of electrically coupled electrode elements disposed on the subject's body and capable of delivering a tumor therapeutic field to the subject's body, wherein at least one of the plurality of electrically coupled electrode elements includes a dielectric layer having a first surface facing the subject's body and a second surface opposite to the first surface, and at least one of the first surface and the second surface of the dielectric layer is a non-planar surface.

[0006] The present invention provides a device for delivering a tumor therapeutic field to a subject's body, the device comprising: an array of connected electrode elements disposed on the subject's body and capable of delivering a tumor therapeutic field to the subject's body, wherein at least one electrode element in the array comprises a ceramic disc, wherein the ceramic disc has a first surface facing the subject's body and a second surface opposite to the first surface, and wherein the ceramic disc has a non-uniform thickness.

[0007] The present invention provides a device for delivering a tumor treatment field to a subject's body, the device comprising: a sensor disposed on the subject's body and capable of delivering a tumor treatment field to the subject's body, wherein the sensor comprises one or more electrode elements having a first surface facing the subject's body and a second surface opposite to the first surface, and wherein at least one of the one or more electrode elements comprises a polymer film having a first surface facing the subject's body and a second surface opposite to the first surface, and wherein the polymer film has a non-uniform thickness. Simple Explanation of the Diagram

[0008] [Figure 1A] is a cross-sectional view of an exemplary embodiment of a sensor having a plurality of coupled electrode elements for delivering a tumor therapeutic field to the body of a subject;

[0009] [Figure 1B] is an enlarged cross-sectional view depicting one of the electrode elements in Figure 1A;

[0010] Figures 2A to 2F are cross-sectional views depicting exemplary embodiments of a dielectric layer structure having a non-planar surface.

[0011] [Figures 3A] to [Figures 3E] are top views depicting an exemplary embodiment of the appearance of a dielectric layer having a non-planar surface when viewed from a direction perpendicular to the surface.

[0012] [Figure 4A] and [Figure 4B] are top views illustrating an exemplary embodiment of the structure of a sensor having a plurality of coupled electrode elements.

[0013] [Figure 5A] and [Figure 5B] are exemplary embodiments depicting the attachment of sensors to a subject's body for the delivery of a tumor treatment field.

[0014] [Figure 6] is a flowchart illustrating an exemplary embodiment of a procedure for manufacturing a device for delivering a tumor treatment field to a subject's body.

[0015] Various embodiments are described in detail below with reference to the accompanying drawings, wherein the same element symbols represent similar elements. Implementation

[0016] The present invention can be more readily understood by referring to the following detailed description, examples, drawings, and claims, as well as the preceding and following description. However, it will be understood that, unless otherwise specified, the present invention is not limited to the specific devices, apparatuses, systems, and / or methods disclosed, and therefore, variations are certainly possible.

[0017] The headings are provided for convenience only and are not intended to be construed as limiting the invention in any way. Embodiments described under any heading or in any part of this disclosure may be combined with embodiments described under the same or any other heading or in other parts of this disclosure.

[0018] Unless otherwise indicated herein or to the contrary, all possible combinations of variations of the elements described herein are encompassed by this invention.

[0019] Unless otherwise expressly stated, no method or feature described herein is intended to be construed as requiring its steps to be performed in a particular order. Therefore, in cases where a method claim does not expressly state in the claim or description that the steps are limited to a particular order, no order is to be inferred in any way. This applies to any possible undefined basis used for interpretation, including logical things related to the configuration of steps or operational flows, general meanings derived from grammatical organization or punctuation, or the number or type of embodiments described in the specification. It will be understood that the foregoing general description and the following detailed description are merely exemplary and illustrative, and not restrictive.

[0020] Some terms will be referenced in this specification and in subsequent requests, and are defined herein.

[0021] As used in the specification and the appended claims, unless the context clearly indicates otherwise, the singular forms “a,” “one,” and “the” refer to a plural number of the objects referred to.

[0022] As used herein, the terms “optional” or “optionally” mean that the event, condition, component or situation described below may or may not occur, and the description includes instances where the event, condition, component or situation occurs and instances where it does not occur.

[0023] As used herein, the term "protrusion" refers to a portion of a surface that extends or projects outward from a surrounding portion of the surface, including, but not limited to, bumps, ridges, or folds. As used herein, the term "notch" refers to a portion of a surface that extends or recesses inward relative to a surrounding portion of the surface, including, but not limited to, dents, depressions, grooves, or folds. As used herein, the term "protrusion or notch" includes both "protrusion and / or notch".

[0024] When an AC voltage is applied to the body, some of that voltage is wasted due to a voltage drop across the dielectric layer of the electrode elements in the sensor. Therefore, a system (device) or method is needed that can deliver maximum voltage to the body without altering the coverage area of ​​the sensor, as the area of ​​the sensor array that can be used for attachment at the desired location on the body is limited. This invention provides a solution to this problem and addresses other important issues.

[0025] When a tumor therapeutic field (TTField) is delivered to a subject's body, an AC voltage of low intensity (e.g., 1 to 4 V / cm) and medium frequency (e.g., 50 to 500 kHz) is applied between sensors, such as capacitors. As described herein, the sensors include electrode elements, which typically include a dielectric layer sandwiched between conductive layers. The latter is configured to function as a capacitor. Capacitance (C) is characterized by the amount of charge (Q) stored per unit voltage (V) between the conductors. Capacitance is inversely proportional to impedance, thus a high capacitance translates to a low impedance, and consequently a correspondingly low voltage drop across the sensor array.

[0026] The inventors have discovered a method for increasing the capacitance of a sensor by utilizing a sensor comprising electrode elements having a dielectric layer with a non-planar surface. Beneath this non-planar surface, the distance between the two surfaces of the dielectric layer becomes non-uniform, and thus the capacitance of the sensor is altered. As described herein, this can improve the electric field power delivered to the subject's body for tumor treatment, and therefore the efficiency of TTField therapy can be improved.

[0027] Figure 1A is a cross-sectional view depicting an exemplary embodiment of a sensor having a plurality of coupled electrode elements for delivering a tumor therapeutic field to a subject's body. In this example, the plurality of electrode elements 101A are integrated into a single sensor 100A.

[0028] Referring to Figure 1A, the electrode element 101A may include a substrate 102A. The substrate 102A is configured for contacting a subject's body or for attaching the sensor 100A to a subject's body for transmitting TTField. Suitable materials for the substrate 102A should be, or contain, conductive materials, and may include, for example, fabrics, foams, and flexible plastics. In one example, the substrate 102A is or contains a conductive medical gel, which may typically have a thickness of about 0.5 mm or greater, or may be injected / absorbed into the substrate material (fabric, foam, flexible plastic, etc.). In a more specific example, the substrate 102A is a layer of conductive hydrogel having a minimum thickness of 0.5 mm. In another example, the substrate 102A is or contains a conductive adhesive, which may typically have a thickness of about 20 µm or greater, or may be injected / absorbed into the substrate material (fabric, foam, flexible plastic, etc.).

[0029] The plurality of electrode elements 101A can be connected to each other via wires 105A. In this example, the plurality of electrode elements 101A are mechanically and electrically connected to each other via the wires 105A. In a different example, the plurality of electrode elements 101A are connected to each other via wires without a substrate 102A.

[0030] In one embodiment, at least one of the plurality of electrode elements 101A includes a dielectric layer 103A. In one embodiment, the dielectric layer 103A has a first surface facing the subject's body and a second surface opposite to the first surface. In the example depicted in FIG1A, the first surface of the dielectric layer 103A is a surface that directly contacts the substrate 102A. In one example, the first surface is a non-planar surface, while the second surface is a substantially planar surface.

[0031] In one embodiment, the dielectric layer 103A is a ceramic layer. In one example, the dielectric layer 103A is a circular ceramic disk. In another example, the dielectric layer 103A is a ceramic element that is not circular or disk-shaped. In yet another example, the dielectric layer 103A is a non-ceramic dielectric material. An example of a non-ceramic dielectric material is one comprising a polymer film or polymer layer.

[0032] In an alternative embodiment, the sensor 100A may comprise only a single electrode element. In one example, the single electrode element may be a flexible organic material or a flexible organic compound disposed on a substrate. In another example, the electrode element may comprise a flexible organic material or a flexible organic compound without a substrate.

[0033] The electrode element 101A may further include a conductive layer 104A. In the example depicted in FIG1A, the conductive layer 104A is in direct contact with the second surface of the dielectric layer 103A. In one example, the conductive layer 104A is a metal layer.

[0034] Other structures for implementing the sensor to replace those used in embodiments of the invention may also be used, provided they are capable of (a) transmitting the TTField to the subject's body and (b) being positioned at the subject's body location. In other embodiments, any electric field generating device may be used in embodiments of the invention, provided that the electric field generating device is capable of transmitting the TTField to the subject's body.

[0035] Figure 1B is an enlarged cross-sectional view depicting an example of the electrode element 101A shown in Figure 1A. In one embodiment, the electrode element 101A includes a substrate 102A, a dielectric layer 103A, and a conductive layer 104A. In one embodiment, the dielectric layer 103A has a first surface 101B facing the subject's body and a second surface 102B opposite to the first surface. In this example, the first surface 101B is in direct contact with the substrate 102A, and the second surface 102B is in direct contact with the conductive layer 104A.

[0036] In one embodiment, the first surface 101B is a non-planar surface, and the second surface 102B is a substantially planar surface. In one example, the first surface 101B is a non-uniform surface or an uneven surface. Therefore, the thickness of the dielectric layer 103A is non-uniform or uneven. The first surface 101B can also be non-uniform or uneven. For example, the non-planar first surface 101B is a surface having at least one protrusion or notch, such as a bump, indentation, depression, ridge, groove, or wrinkle, or similar, or a combination thereof. In one example, the non-planar first surface 101B is a surface having both a protrusion and a notch. In one example, the non-planar first surface 101B is a chemically etched surface having at least one protrusion or notch. In another example, the non-planar first surface 101B is cut using a cutting tool, laser, or water jet. In another example, the non-planar first surface 101B is embossed or molded.

[0037] In another embodiment, the non-planar first surface 101B is a surface having a plurality of sidewalls 103B. In one example, the plurality of sidewalls 103B are the sides of at least one protrusion or recess of the non-planar first surface 101B. In one example, when viewed from a cross-sectional direction, the plurality of sidewalls 103B includes at least two substantially vertical sidewalls, at least two curved or arcuate sidewalls, at least two inclined sidewalls, at least two trapezoidal sidewalls, or a combination thereof. Examples of these embodiments are further depicted in Figures 2A to 2F, which are discussed further below.

[0038] In another embodiment, when viewed from a direction perpendicular to the first surface, the protrusions or recesses of the non-planar surface 101B are configured in a pattern. For example, when viewed from a direction perpendicular to the first surface, the protrusions or recesses of the non-planar first surface 101B are configured as at least two substantially parallel lines, at least two substantially perpendicular lines, at least two substantially concentric circles, at least two circles of substantially similar size, or at least two substantially similar square or rectangular shapes, or a combination thereof. In another embodiment, when viewed from a direction perpendicular to the first surface, the protrusions or recesses of the non-planar surface 101B are configured in a random manner. Examples of these embodiments are further depicted in Figures 3A to 3E, which are discussed further below.

[0039] In another embodiment, the distance between the first surface 101B and the second surface 102B of the dielectric layer 103A is non-uniform. In the example depicted in FIG1B, the distance between the first surface 101B and the second surface 102B includes: a first distance d1 between the top of the protrusion and the second surface 102B; and a second distance d2 between the bottom of the protrusion on the first surface 101B and the second surface 102B. In this example, d2 is less than d1. In one example, the difference between d1 and d2 is less than or equal to 30% of d1. In another example, the difference between d1 and d2 is less than or equal to 20% of d1, or less than or equal to 10% of d1.

[0040] Maximizing the voltage delivered to the body can be achieved by minimizing the voltage wasted due to a voltage drop across the dielectric layer of the electrode elements in the sensor. Since voltage and capacitance are inversely proportional in a capacitor, the latter (minimizing the voltage drop) can be achieved by maximizing the capacitance in the electrode elements of the sensor.

[0041] In general, the capacitance of the dielectric layer can be calculated using the following equation: C = εA / d Equation 1 Where ε is the absolute dielectric constant of the dielectric material; A is the surface area of ​​the two parallel surfaces of the dielectric layer; and d is the distance between the two surfaces of the dielectric layer.

[0042] Assuming the surface area and absolute dielectric constant of the dielectric layer remain constant, reducing the distance d between the conductive layers (i.e., reducing the thickness of the dielectric layer) will increase the capacitance. In Figure 1B, reducing the overall layer thickness from d1 to d2 will increase the capacitance. At the lower limit of the thickness d2, the dielectric layer may be too fragile and lack durability for the desired application, but at the larger thickness d1, the durability can be improved and may be sufficiently usable. Figure 1B depicts the use of protrusions in the dielectric layer 103A to increase the layer thickness in the region of the protrusions to the larger thickness d1, in order to restore some of the durability characteristics of the thicker dielectric layer. For the simplified stepped protrusion / notch in Figure 1B with only two distances (dielectric layer thicknesses) d1 and d2, the sum of all areas at distance d1 (observed perpendicular to the XY plane) is A1, and the sum of all areas at distance d2 (observed perpendicular to the XY plane) is A2. The total capacitance Ctotal = C1 + C2, where: C 1 = εA 1 / d 1 and C² = εA² / d²

[0043] Therefore, the capacitance of the dielectric layer at the smaller thickness (distance d2) is greater than that at the distance d1 (because the capacitance is inversely proportional to the distance (dielectric thickness)). In this respect, the overall capacitance of the dielectric layer is increased by having a non-planar first surface compared to a dielectric layer with a thickness d1. Furthermore, the improvement in capacitance is further enhanced because the capacitance is proportional to the surface area of ​​the dielectric layer, which is greatly increased by including the protrusions / notches on the surface of the dielectric layer (the surface area is increased, for example, by the additional sidewalls of the notches and the protruding surfaces of the protrusions).

[0044] Figures 2A to 2F are cross-sectional views depicting an exemplary embodiment of a dielectric layer structure having a non-planar surface.

[0045] Figure 2A illustrates an example of the structure of the dielectric layer. In this example, the dielectric layer has a first non-planar surface 201A and a second substantially planar surface 202A. In one embodiment, the first non-planar surface 201A has one or more protrusions (bumps) 203A. In one example, the one or more protrusions 203A have at least two vertical sidewalls 204A. The term "vertical" refers to a direction that is perpendicular or substantially perpendicular (e.g., within + / - 10 degrees of verticality) to the first surface.

[0046] Figure 2B illustrates another example of the structure of the dielectric layer. In this example, the dielectric layer has a first non-planar surface 201B and a second substantially planar surface 202B. In one embodiment, the first non-planar surface 201B has one or more substantially arcuate notches 203B. In one example, the one or more substantially arcuate notches 203B have at least two curved sidewalls 204B.

[0047] Figure 2C illustrates another example of the structure of the dielectric layer. In this example, the dielectric layer has a first non-planar surface 201C and a second substantially planar surface 202C. In one embodiment, the first non-planar surface 201C has one or more substantially triangular notches (grooves) 203C. In one example, the one or more substantially triangular notches 203C have two inclined sidewalls 204C.

[0048] Figure 2D illustrates another example of the structure of the dielectric layer. In this example, the dielectric layer has a first non-planar surface 201D and a second substantially planar surface 202D. In one embodiment, the first non-planar surface 201D has one or more notches 203D. In one example, the one or more notches 203D have at least two trapezoidal sidewalls 204D.

[0049] Figure 2E illustrates another example of the structure of the dielectric layer. In this example, the dielectric layer has a first non-planar surface 201E and a second substantially planar surface 202E. In one embodiment, the first non-planar surface 201E has one or more alternating protrusions-notches (wrinkles) 203E.

[0050] Figure 2F illustrates another example of the structure of the dielectric layer. In this example, the dielectric layer has a first non-planar surface 201F and a second substantially planar surface 202F. In one embodiment, the first non-planar surface 201F has a random surface structure of protrusions and notches, such as troughs, crests, slopes, curves, walls, etc.

[0051] It will be understood that the embodiments described herein are not intended to be limiting, as other protrusions / notches are obviously possible. Furthermore, there are embodiments in which the second surface is non-planar, being additional to or alternative to the first non-planar surface, and such protrusions / notches may exist on the second surface in these embodiments.

[0052] Figures 3A to 3E illustrate examples of the appearance of the non-planar first surface of the dielectric layer when viewed from a direction perpendicular to the non-planar surface. In Figures 3A to 3E, the protrusions and notches of the non-planar first surface are configured in a pattern when viewed from a direction perpendicular to the first surface. However, it should be noted that in some other embodiments, the protrusions and notches of the non-planar first surface may be configured in a random manner when viewed from a direction perpendicular to the first surface.

[0053] Figure 3A is an example depicting the appearance of the non-planar first surface. In this example, the first non-planar surface 301A is depicted by at least two substantially parallel lines 302A representing the protrusions and / or recesses of the non-planar first surface.

[0054] Figure 3B is another example depicting the appearance of the non-planar first surface. In this example, the first non-planar surface 301B is depicted by at least two substantially perpendicular lines 302B and 303B depicting the protrusions and / or notches of the non-planar first surface.

[0055] Figure 3C is another example depicting the appearance of the non-planar first surface. In this example, the first non-planar surface 301C is depicted as at least two substantially concentric circles 302C representing the protrusions and / or recesses of the non-planar first surface.

[0056] Figure 3D is another example depicting the appearance of the non-planar first surface. In this example, the first non-planar surface 301D is a circle 302D depicting the protrusions and / or recesses of the non-planar first surface as at least two substantially similar sizes.

[0057] Figure 3E is another example depicting the appearance of the non-planar first surface. In this example, the first non-planar surface 301E is depicted as a rod-shaped rectangle 302E with at least two substantially similar dimensions for the protrusions and / or recesses of the non-planar first surface. In other embodiments, the protrusions and / or recesses of the non-planar first surface may be square or other polygonal shapes with at least two substantially similar dimensions.

[0058] Figures 4A and 4B are top views illustrating an exemplary embodiment of the structure of a sensor having a plurality of coupled electrode elements. For example, as shown in Figure 4A, the sensor 400A has a substrate 402A and a plurality of electrode elements 401A. The substrate 402A is configured for attaching the sensor to the body of a subject. Suitable materials for the substrate 402A include, for example, fabrics, foams, and flexible plastics. In some embodiments, the substrate 402A comprises a conductive medical gel having a thickness of not less than about 0.5 mm, or a conductive adhesive having a thickness of not less than 20 µm. In a more specific example, the substrate 402A is a hydrogel having a minimum thickness of about 0.5 mm. In this case, the sensor 400A is attached to the body of the subject through the substrate 402A.

[0059] A plurality of capacitively coupled electrode elements 401A are positioned on the substrate 402A, and each of the capacitively coupled electrode elements has a conductive plate on which a dielectric layer is disposed, facing the substrate. In one embodiment, the dielectric layer has a first surface facing the subject's body and a second surface opposite to the first surface. In one example, the dielectric layer has a first surface contacting the substrate and a second surface contacting the conductive plate. In some examples, at least one of the plurality of electrode elements has a dielectric layer with a non-planar surface. For example, the non-planar surface may be the first surface of the dielectric layer. Alternatively, one or more sensors may be disposed below each of the electrode elements in a manner similar to that known in the NovocureOptune® system. In one example, the one or more sensors are temperature sensors (e.g., thermistors).

[0060] In some embodiments, the plurality of electrode elements 401A are substantially flat electrode elements. In one example, the dielectric layer of the electrode element is a circular dielectric layer. In a more specific example, the dielectric layer is a ceramic disk, and each of the ceramic disks is approximately 2 cm in diameter and approximately 1 mm in maximum thickness. In other embodiments, the dielectric layer is a non-circular dielectric layer. In other embodiments, the dielectric layer is a non-disc-shaped ceramic element.

[0061] Figure 4B illustrates an example of a sensor 400B having electrode elements 401B with non-ceramic coupling. In this example, the sensor 400B has a substrate 402B and a plurality of electrode elements 401B, each electrode element comprising a non-ceramic dielectric layer. In one embodiment, the non-ceramic dielectric layer comprises a flexible dielectric material. Examples of flexible dielectric materials include dielectric polymers or dielectric copolymers. In some embodiments, the non-ceramic dielectric layer 401B is non-circular in shape. In Figure 4B, the electrode element 401B (and the polymer dielectric layer) is substantially triangular or wedge-shaped, although in other embodiments, the non-ceramic dielectric layer (e.g., a polymer layer) can be of any shape. In some examples, the non-ceramic dielectric layer has a maximum thickness of approximately 1 mm or less. In another embodiment, the sensor 400B does not include a substrate. In this embodiment, the non-ceramic dielectric layer can be directly attached to the body of a subject, optionally via a layer of hydrogel or a conductive adhesive.

[0062] The dielectric layer may have a first surface facing the subject's body and a second surface opposite to the first surface. In one example, the dielectric layer has a first surface contacting the substrate and a second surface contacting a conductive material. In some embodiments, at least one of the plurality of electrode elements has a dielectric layer having at least one non-planar surface. In some embodiments, at least one of the plurality of electrode elements has a dielectric layer having a non-planar first surface.

[0063] Sensors utilizing an array of non-capacitively coupled electrode elements can also be used. In this case, the sensors 400A and 400B can be implemented using a region of conductive material, configured to be placed against the body of a subject, wherein no insulating dielectric layer is disposed between the conductive elements and the body.

[0064] Figures 5A and 5B are exemplary embodiments depicting the sensor attached to the subject's body for delivering a tumor treatment field.

[0065] In the example depicted in Figure 5A, sensors 501A, 502A, 503A, and 504A are attached to the head of a subject to apply a TTField to the subject's head. In one embodiment, two electric fields are alternately applied between two pairs of sensors. Each pair of sensors is a channel applied to generate a TTField in the subject's body. As for the paired sensors, sensors 501A and 503A may form a first pair of sensors, and sensors 502A and 504A may form a second pair of sensors.

[0066] In this example, a first tumor treatment electric field (TTField) between the first pair of sensors and a second tumor treatment electric field (TTField) between the second pair of sensors are generated alternately. The first TTField is generated between the first pair of sensors by applying a first AC voltage generated by a first AC generator during a first time period, and has, for example, a low intensity (e.g., 1 to 4 V / cm) and a mid-frequency range (e.g., 50 to 576 kHz, or in some cases, 125 to 250 kHz). In one example, the frequency of the first TTField is 150 kHz. The first AC voltage is applied to the first pair of sensors during the first time period (e.g., one second). After the first time period, the generation of the first TTField is stopped. Then, the second TTField is generated between the second pair of sensors by applying a second AC voltage generated by a second AC generator during a second time period, and has, for example, a low intensity (e.g., 1 to 4 V / cm) and a mid-frequency range (e.g., 50 to 576 kHz, or in some cases, 125 to 250 kHz). In one example, the frequency of the second TTField is 150 kHz. The second AC voltage is applied to the second pair of sensors during the second time period (e.g., one second). The second time period and the first time period can be the same or different. After the second time period, the generation of the second TTField is stopped. The method then alternately repeats the procedure of generating the first TTField between the first pair of sensors during the first time period and generating the second TTField between the second pair of sensors during the second time period.

[0067] In the example depicted in Figure 5B, sensors 501B, 502B, 503B, and 504B are attached to a subject's body to apply a TTField to the subject's torso. In one embodiment, two electric fields are applied alternately between two pairs of sensors. Each pair of sensors is a channel applied to generate a TTField in the subject's body. In the example depicted in Figure 5B, sensor 501B is attached to the front of the subject's right chest, sensor 502B is attached to the front of the subject's right thigh, sensor 503B is attached to the back of the subject's left chest, and sensor 504B is attached to the back of the subject's left thigh. As for the paired sensors, sensors 501B and 504B can form a first pair of sensors, and sensors 502B and 503B can form a second pair of sensors.

[0068] Figure 6 is a flowchart illustrating an exemplary embodiment of a procedure for manufacturing a device for delivering a tumor treatment field to a subject's body.

[0069] Referring to Figure 6, in step S602, the method includes producing a ceramic disk. In some embodiments, the ceramic disk includes a dielectric material. The ceramic disk has a first surface and a second surface, and the first surface is a non-planar surface. In one embodiment, the method further includes chemically etching or cutting the first surface of the ceramic disk to produce the non-planar surface. In some examples, the first surface of the ceramic disk is cut using a cutting tool, a laser, or a water jet. In other embodiments, the method includes imprinting or molding the first surface of the ceramic disk to produce the non-planar surface.

[0070] In step S604, the method includes attaching a conductive material to the second surface of the ceramic disk. In some embodiments, the second surface of the ceramic disk is substantially planar. In one example, the conductive material is a metal. In a more specific example, the conductive material is a metal layer.

[0071] In step S606, the method includes coupling the ceramic disk and other ceramic disks to form an array of ceramic disks capable of delivering the TTField to the subject's body. In some embodiments, one or more of the other ceramic disks have a non-planar first surface. In other embodiments, one or more of the other ceramic disks have two substantially planar surfaces.

[0072] Figure 6 illustrates a method for manufacturing an array of ceramic discs according to an embodiment of the present invention. In other embodiments of the invention, similar manufacturing methods can be used to produce an array of electrodes comprising a polymer film. To obtain one or more non-planar surfaces on the polymer film, the surfaces of the polymer film can be embossed or molded. For example, the first surface of the polymer film can be embossed or molded. Exemplary Examples

[0073] The present invention includes other exemplary embodiments, such as the following.

[0074] Exemplary Example 1: A device for delivering a tumor therapeutic field to the body of a subject, the device comprising: a plurality of electrically coupled electrode elements disposed on the body of a subject and capable of delivering a tumor therapeutic field to the body of the subject, wherein at least one of the plurality of electrically coupled electrode elements includes a dielectric layer having a first surface facing the body of the subject and a second surface opposite to the first surface, and at least one of the first surface and the second surface of the dielectric layer is a non-planar surface.

[0075] Example 2: The device as in Example 1, wherein the first surface of the dielectric layer is non-planar and the second surface of the dielectric layer is substantially planar.

[0076] Example 3: The device as in Example 2, wherein the non-planar first surface is a surface having at least one protrusion or notch.

[0077] Exemplary Example 4: The device as in Exemplary Example 3, wherein the non-planar first surface is a chemically etched surface having at least one protrusion or notch.

[0078] Exemplary Embodiment 5: The device as in Exemplary Embodiment 3, wherein, when viewed from a direction perpendicular to the first surface, the protrusions or recesses of the non-planar first surface are configured as a pattern.

[0079] Example 6: The device as in Example 3, wherein, when viewed from a direction perpendicular to the first surface, the protrusions or recesses of the non-planar first surface are configured as at least two substantially parallel lines, at least two substantially perpendicular lines, at least two substantially concentric circles, at least two substantially similar-sized circles, or at least two substantially square or rectangular shapes, or a combination thereof.

[0080] Exemplary Embodiment 7: The device as in Exemplary Embodiment 3, wherein, when viewed from a direction perpendicular to the first surface, the protrusions or recesses of the non-planar first surface are configured in a random manner.

[0081] Exemplary Embodiment 8: The device as in Exemplary Embodiment 2, wherein the non-planar first surface is a surface having a plurality of sidewalls, and wherein the plurality of sidewalls includes at least two vertical sidewalls, at least two curved sidewalls, at least two inclined sidewalls, at least two trapezoidal sidewalls, or a combination thereof.

[0082] Exemplary Example 9: The device as in Exemplary Example 2, wherein the at least one electrode element comprises a circular ceramic disk.

[0083] Example 10: The device as in Example 2, wherein the at least one electrode element comprises a polymer film or polymer layer.

[0084] Exemplary Example 11: The device as in Exemplary Example 2, wherein the at least one electrode element is non-circular in shape.

[0085] Exemplary Embodiment 12: The device as in Exemplary Embodiment 2, wherein the at least one electrode element further comprises: a substrate in direct contact with the first surface of the dielectric layer; and a conductive layer in direct contact with the second surface of the dielectric layer.

[0086] Exemplary Example 13: The device as in Exemplary Example 12, wherein the substrate is in contact with or attached to the body of the subject when delivering a tumor treatment field.

[0087] Exemplary Example 14: The device as in Exemplary Example 2, wherein the at least one electrode element further comprises a hydrogel or a conductive adhesive on the first surface of the dielectric layer.

[0088] Exemplary Example 15: The device as in Exemplary Example 2, wherein the at least one electrode element further includes a metal layer on the second surface of the dielectric layer.

[0089] Exemplary Embodiment 16: The device as in Exemplary Embodiment 1, wherein the first surface of the dielectric layer is non-planar, the second surface of the dielectric layer is substantially planar, and wherein a distance between the non-planar first surface and the substantially planar second surface is non-uniform and varies less than or equal to 30%.

[0090] Exemplary Example 17: The device as in Exemplary Example 1, wherein the electrode element is capacitively coupled.

[0091] Exemplary Example 18: The device as in Exemplary Example 1, wherein the electrode elements are not capacitively coupled.

[0092] Exemplary Example 19: A device for delivering a tumor therapeutic field to the body of a subject, the device comprising: an array of connected electrode elements disposed on the body of a subject and capable of delivering a tumor therapeutic field to the body of the subject, wherein at least one electrode element of the array comprises a ceramic disk having a first surface facing the body of the subject and a second surface opposite to the first surface, and wherein the ceramic disk has a non-uniform thickness.

[0093] Exemplary Example 20: The device as in Exemplary Example 19, wherein, when viewed in cross-section, the first surface of the ceramic disc has a non-uniform surface.

[0094] Exemplary Example 21: The device as in Exemplary Example 19, wherein, when viewed in cross-section, the first surface of the ceramic disc has an uneven surface.

[0095] Exemplary Example 22: A device for delivering a tumor treatment field to the body of a subject, the device comprising: a sensor disposed on the body of a subject and capable of delivering a tumor treatment field to the body of the subject, wherein the sensor includes one or more electrode elements having a first surface facing the body of the subject and a second surface opposite to the first surface, and wherein at least one of the electrode elements includes a polymer film having a first surface facing the body of the subject and a second surface opposite to the first surface, and wherein the polymer film has a non-uniform thickness.

[0096] Exemplary Example 23: The apparatus of Exemplary Example 22, wherein, when viewed in cross-section, the first surface of the polymer film has a non-uniform surface.

[0097] Exemplary Example 24: The apparatus as in Exemplary Example 22, wherein, when viewed in cross-section, the first surface of the polymer film has an uneven surface.

[0098] Exemplary Example 25: A method of manufacturing a device for delivering a tumor therapeutic field to the body of a subject, the method comprising: producing a ceramic disk including a dielectric material capable of delivering a tumor therapeutic field to the body of the subject, the ceramic disk having a first surface facing the body of the subject and a second surface opposite to the first surface, the first surface of the ceramic disk being a non-planar surface; attaching a conductive material to the second surface of the ceramic disk; and coupling the ceramic disk and other ceramic disks to form an array of ceramic disks capable of delivering a tumor therapeutic field to the body of the subject.

[0099] Exemplary Example 26: The method of Exemplary Example 25 further includes chemically etching or cutting the first surface of the ceramic disk to produce the non-planar surface.

[0100] Exemplary Example 27: The method of Exemplary Example 25, wherein the first surface of the ceramic disc is cut using a cutting tool, a laser, or a water jet.

[0101] Although the invention has been disclosed with reference to certain embodiments, many modifications, alterations, and variations of the said embodiments are possible without departing from the scope and range of the invention as defined in the appended claims. Therefore, it is desired that the invention is not limited to the said embodiments, but rather has the broadest scope defined by the language of the following claims and their equivalents.

[0102] 100A: Sensor 101A: Electrode element 101B: First Surface 102A:Substrate 102B: Second Surface 103A: Dielectric layer 103B: Sidewall 104A: Conductive layer 105A: Conductor 201A: The first non-planar surface 201B: First non-planar surface 201C: First non-planar surface 201D: The first non-planar surface 201E: First non-planar surface 201F: The first non-planar surface 202A: Surface of the second substantial plane 202B: Surface of the second substantial plane 202C: Surface of the second substantial plane 202D: Surface of the second substantial plane 202E: Surface of the second substantial plane 202F: Surface of the second substantial plane 203A: Protrusion / Bump 203B: Notch of a solid circular arc 203C: Substantial triangular notch / groove 203D: Notch 203E: Alternating protrusions - notches / wrinkles 204A: Vertical sidewalls 204B: Curved sidewalls 204C: Sloping sidewalls 204D: Trapezoidal sidewalls 301A: First non-planar surface 301B: First non-planar surface 301C: First non-planar surface 301D: The first non-planar surface 301E: First non-planar surface 302A: Lines that are substantially parallel 302B: A line that is substantially perpendicular 302C: Concentric circles in substance 302D: A circle of substantially similar size 302E: A rod-shaped rectangle of substantially similar size 303B: A line that is substantially perpendicular 400A: Sensor 400B: Sensor 401A: Electrode element 401B: Electrode Elements 402A:Substrate 402B:Substrate 501A, 501B: Sensors 502A, 502B: Sensors 503A, 503B: Sensors 504A, 504B: Sensors S602: Steps S604: Steps S606: Steps d1: First distance d2: Second distance

Claims

1. A device for delivering a tumor treatment field to the body of a subject, the device comprising: A plurality of electrically coupled electrode elements are disposed on the body of a subject and are capable of delivering a tumor therapeutic field to the subject's body. At least one of the plurality of electrically coupled electrode elements includes a dielectric layer having a first surface facing the subject's body and a second surface opposite to the first surface. At least one of the first surface and the second surface of the dielectric layer is a non-planar surface, such that the distance between the first surface and the second surface of the dielectric layer becomes non-uniform, thereby altering the capacitance of the sensor formed by the plurality of electrically coupled electrode elements.

2. The device of claim 1, wherein the first surface of the dielectric layer is non-planar and the second surface of the dielectric layer is substantially planar.

3. The device of claim 2, wherein the non-planar first surface is a surface having at least one protrusion or notch.

4. The equipment as requested in item 3, wherein, When viewed from a direction perpendicular to the first surface, the protrusions or recesses on the non-planar first surface are configured as a pattern.

5. The equipment as requested in item 3, wherein, When viewed from a direction perpendicular to the first surface, the protrusions or recesses of the non-planar first surface are configured as at least two substantially parallel lines, at least two substantially perpendicular lines, at least two substantially concentric circles, at least two substantially similar-sized circles, or at least two substantially square or rectangular shapes.

6. The equipment as requested in item 3, wherein, When viewed from a direction perpendicular to the first surface, the protrusions or recesses on the non-planar first surface are arranged in a random manner.

7. The device of any one of claims 1 to 6, wherein the non-planar first surface is a surface having a plurality of sidewalls, and wherein said plurality of sidewalls includes at least two vertical sidewalls, at least two curved sidewalls, at least two inclined sidewalls, and at least two trapezoidal sidewalls.

8. The device of any one of claims 1 to 6, wherein the at least one electrode element comprises a circular ceramic disk.

9. The apparatus of any one of claims 1 to 6, wherein the at least one electrode element comprises a polymer film or a polymer layer.

10. The apparatus of any one of claims 1 to 6, wherein said at least one electrode element further comprises: A substrate that is in direct contact with the first surface of the dielectric layer; And a conductive layer that directly contacts the second surface of the dielectric layer.

11. The device of any one of claims 1 to 6, wherein the first surface of the dielectric layer is non-planar, the second surface of the dielectric layer is substantially planar, and wherein the distance between the non-planar first surface and the substantially planar second surface is non-uniform and varies by less than or equal to 30%.

12. A device for delivering a tumor treatment field to the body of a subject, the device comprising: An array of connected electrode elements, disposed on a subject's body and capable of delivering a tumor therapeutic field to the subject's body, wherein at least one electrode element in the array comprises a ceramic disc, wherein the ceramic disc has a first surface facing the subject's body and a second surface opposite to the first surface, and wherein the ceramic disc has a non-uniform thickness such that the distance between the first surface and the second surface of the ceramic disc becomes non-uniform, thereby altering the capacitance of the sensor formed by the array of connected electrode elements.

13. The equipment as requested in item 12, wherein, When viewed in cross-section, the first surface of the ceramic disc has a non-uniform surface.

14. A device for delivering a tumor treatment field to the body of a subject, the device comprising: A sensor, which is disposed on the body of a subject and is capable of transmitting a tumor therapeutic field to the subject's body, wherein the sensor includes one or more electrode elements having a first surface facing the subject's body and a second surface opposite to the first surface, and wherein at least one of the one or more electrode elements includes a polymer film having a first surface facing the subject's body and a second surface opposite to the first surface, and wherein the polymer film has a non-uniform thickness such that the distance between the first surface and the second surface of the polymer film becomes non-uniform, thereby altering the capacitance of the sensor.

15. The equipment as requested in item 14, wherein, When viewed in cross-section, the first surface of the polymer film has a non-uniform surface.

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